Objectives. Osteoarthritis (OA) is the most common form of arthritis, affecting approximately 15% of the human population. Recently, increased concentration of nitric oxide in serum and synovial fluid in patients with OA has been observed. However, the exact role of nitric oxide in the initiation of OA has not been elucidated. The aim of the present study was to investigate the role of nitric oxide in innate immune regulation during OA initiation in rats. Methods. Rat OA was induced by performing meniscectomy surgery while cartilage samples were collected 0, 7, and 14 days after surgery. Cartilage cytokine levels were determined by using enzyme-linked immunosorbent assay, while other proteins were assessed by using Western blot. Results. In the time course of the study, nitric oxide was increased seven and 14 days after OA induction. Pro-inflammatory cytokines including tumour necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were decreased. L-NG-Nitroarginine methyl ester (L-NAME, a non-specific nitric oxide synthase inhibitor) significantly decreased cartilage nitric oxide and blocked immune suppression. Further, L-NAME decreased Matrix metalloproteinase (MMPs) and increased tissue inhibitor of metalloproteinase (TIMP) expression in meniscectomised rats. Conclusion. Nitric oxide-dependent innate immune suppression protects cartilage from damage in the early stages of OA initiation in rats. Cite this article: C-C. Hsu, C-L. Lin, I-M. Jou, P-H. Wang, J-S. Lee. The protective role of nitric oxide-dependent innate immunosuppression in the early stage of cartilage damage in rats: Role of nitric oxide in ca rtilage da mage. Bone Joint Res 2017;6:253–258. DOI: 10.1302/2046-3758.64.BJJ-2016-0161.R1

The incidence of osteoarthritis (OA) is increasing in our younger population. OA development early in life is often related to cartilage damage, caused by (sport) injury or trauma. Detection of early knee OA is therefore crucial to target early treatment. However, early markers for OA prognosis or diagnosis are lacking. Hoffa's fat pad (HFP) is an emerging source for knee biomarkers, as it is easily accessible and shows important interaction with the homeostasis of the knee. In this study, we used Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) as a first approach. MALDI-MSI allows the study of tissue-specific molecular distributions. Therefore, we used MALDI-MSI to analyze the lipid profiles in the HFP of three patients with OA and three patients undergoing cartilage regenerative treatment. We demonstrate that the lipid profile of patients with OA is different from patients with cartilage defects. HFP of each patient were snap frozen directly after surgical resection and cryosectioned at 15 μm. Each slide was sublimed with Norharmane matrix and analyzed by MALDI-MSI in positive and negative ion modes at a lateral resolution of 50 μm on a RapifleX Tissue Typer. The difference between patient groups were analyzed using principle component analysis and linear discriminant analysis. Lipid identifications were obtained on an Orbitrap Elite™ Hybrid Ion Trap-Orbitrap Mass Spectrometer in data dependent acquisition mode and analyzed using Lipostar software. Linear discriminant analysis showed a specific lipid profile for each group (variance 33.94%). Score projections revealed a differential lipid spatial distribution of OA patients compared to cartilage defect patients. Among the lipids that differed significantly, for instance, the m/z 760.59 [M+H]. +. was associated to osteoarthritis and identified as glycerophospholipid (PC 34:1), a main component of biological membranes. Additionally, the samples were found to be intra-tissue heterogeneous, with molecular profiles found in adipose-, connective- and synovial tissue. These results suggest that lipid profiles in HFP could be useful for early OA detection. However, intra-tissue heterogeneity in HFP should be recognized when using HFP as a biomarker source

Femoroacetabular impingement recently was recognized as cause for osteoarthritis of the hip. There are two mechanism of impingement: (1) cam impingement caused by a non-spherical head, and (2) pincer impingement due to acetabular overcover. We hypothesized that both mechanism result in different articular damage patterns. Of 302 analyzed hips only 26 had an isolated cam and 16 an isolated pincer impingement. Cam impingement caused anterosuperior acetabular cartilage damage with a separation between labrum and cartilage. During flexion the cartilage is sheared off the bone by the non-spherical part of the femoral head. In pincer impingement the cartilage damage was located circumferentially, invovolving only a narrow strip along the acetabular rim. During motion the labrum is crushed between the acetabular rim and the femoral neck causing degeneration and ossification of the labrum. Cam and pincer impingement are two basic mechanism that lead to osteoarthrosis of the hip. The articular damage pattern differs substantially. Isolated cam or pincer impingement is rare, in most hips a combination is present. Labral damage indicates ongoing impingement and rarely occurs alone

Purpose: Use of autologous chondrocyte grafts for the treatment of knee cartilage damage appears to be a promising solution. We report preliminary retrospective results in 15 autologous chondrocyte grafts with maximum 4.1 years follow-up. Material and methods: From September 1996 to December 2000, 15 autologous chondrocyte grafts were performed in 15 patients (13 men and two women), mean age 29.1 years (14.2–46.5) using the Carticel procedure of the Genzyme Tissue Repair laboratory. There were ten trauma-induced chondral lesions and five cases of osteochondritis dessicans. The lesions were located in the femoral condyles in 14 cases (12 medial and two lateral) and the patella in one. Mean surface defect was 6 cm2 (1–15) and all lesions were ICRS grade 3 or 4. The technique described by Brittberg et al. was used. Harvested cartilage was sent to Cam-bridge (USA) for culture. Reimplantation, performed by arthrotomy in all cases, was achieved 12 weeks on average (3.5–29) after initiating culture. Clinical and laboratory results at last follow-up were compared with preoperative data using the ICRS evaluation chart and the Tegner, IKDC, modified Cincinnati, and Lysholm scores. Patients were followed regularly with x-rays, MRI or arthroscan. Results: Mean follow-up was 2.5 years (1.2–4.1). The subjective IKDC, modified Cincinnati, and Lysholm scores progressed respectively from 38.3 (9–46) to 71.3 (24–98), from 31.6 (18–69) to 58.4 (26–97) and from 41.9 (13–61) to 81.3 (29–100). According to this classification, outcome was excellent or good in ten knees, fair in four and poor in one. For the activity level assessed by the ICRS and Tegner classifications, scores declined respectively from 2.2 (1–3) and 7.4 (5–10) preoperatively to 2.8 (2–4) and 5.2 (2–7) at last follow-up. Discussion: Due to the small number of patients, it is difficult to compare our results with those reported in the literature. Clinical and functional improvement appeared to be significant but in our experience, there was a decline in the mean sports level at last follow-up. Conclusion: Autologous chondrocyte grafting appears to be a promising technique for repairing cartilage damage. Use of second-generation grafts with chondrocytes embedded in a solid matrix should facilitate their surgical implantation and improve outcome

Aims. The metabolic variations between the cartilage of osteoarthritis (OA) and Kashin-Beck disease (KBD) remain largely unknown. Our study aimed to address this by conducting a comparative analysis of the metabolic profiles present in the cartilage of KBD and OA. Methods. Cartilage samples from patients with KBD (n = 10) and patients with OA (n = 10) were collected during total knee arthroplasty surgery. An untargeted metabolomics approach using liquid chromatography coupled with mass spectrometry (LC-MS) was conducted to investigate the metabolomics profiles of KBD and OA. LC-MS raw data files were converted into mzXML format and then processed by the XCMS, CAMERA, and metaX toolbox implemented with R software. The online Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to annotate the metabolites by matching the exact molecular mass data of samples with those from the database. Results. A total of 807 ion features were identified for KBD and OA, including 577 positive (240 for upregulated and 337 for downregulated) and 230 negative (107 for upregulated and 123 for downregulated) ions. After annotation, LC-MS identified significant expressions of ten upregulated and eight downregulated second-level metabolites, and 183 upregulated and 162 downregulated first-level metabolites between KBD and OA. We identified differentially expressed second-level metabolites that are highly associated with cartilage damage, including dimethyl sulfoxide, uric acid, and betaine. These metabolites exist in sulphur metabolism, purine metabolism, and glycine, serine, and threonine metabolism. Conclusion. This comprehensive comparative analysis of metabolism in OA and KBD cartilage provides new evidence of differences in the pathogenetic mechanisms underlying cartilage damage in these two conditions. Cite this article: Bone Joint Res 2024;13(7):362–371

INTRODUCTION. Mobile bearing unicompartmental knee replacement (UKR) is an accepted treatment for patients with isolated medial unicompartmental knee osteoarthritis (OA) with a full thickness cartilage loss. The aim of this study was to determine if this recommendation was correct and if the procedure could be used for partial-thickness cartilage loss. METHODS. 1053 Oxford medial UKRs were studied prospectively. The knees were divided into two groups; partial-thickness cartilage loss (PTCL) group and the full thickness-cartilage loss (FTCL) group. The primary outcome measure was the total Oxford Knee Score (OKS, 0 to 48) at the time of final follow up. The groups were also compared for the change in OKS (?OKS) and the proportion of patients that were considered to have benefited substantially from surgery (?OKS >5). RESULTS. There were 21 knees in the PTCL group, with a mean age of 61 years (SD 13) and mean follow-up of 1.7 years (SD 1.0). There were 1032 knees in the FTCL group, with a mean age of 66 years (SD 10) and mean follow-up of 3.9 years (SD 2.5). The PTCL group had a significantly lower (p=0.03) total OKS (mean 35.8, SD 10.7) at final review than the FTCL group (mean 39.8, SD 8.5). There was no significant difference in pre-operative or ?OKS between the groups. However the proportion of patients that did not have substantial benefit from surgery (?OKS>5) was significant lower (p=0.04) in the PTCL group. CONCLUSIONS. The results confirm that a good outcome can routinely be achieved with UKR if there is bone-on-bone. If there is partial loss of cartilage the results are less predictable. Although some patients do well, a higher proportion do not benefit from the surgery. It may be that in a subgroup of these patients the pain did not initially arise from the partially damaged cartilage. We therefore recommend that the Oxford Knee should only be used for medial OA if there is bone on bone

Aims. Mesenchymal stem cells (MSCs) are usually cultured in a normoxic atmosphere (21%) in vitro, while the oxygen concentrations in human tissues and organs are 1% to 10% when the cells are transplanted in vivo. However, the impact of hypoxia on MSCs has not been deeply studied, especially its translational application. Methods. In the present study, we investigated the characterizations of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in hypoxic (1%) and normoxic (21%) atmospheres with a long-term culture from primary to 30 generations, respectively. The comparison between both atmospheres systematically analyzed the biological functions of MSCs, mainly including stemness maintenance, immune regulation, and resistance to chondrocyte apoptosis, and studied their joint function and anti-inflammatory effects in osteoarthritis (OA) rats constructed by collagenase II. Results. We observed that long-term hypoxic culture surpassed normoxic atmosphere during hUC-MSCs culture in respect of promoting proliferation, anti-tumorigenicity, maintaining normal karyotype and stemness, inhibiting senescence, and improving immunoregulatory function and the role of anti-apoptosis in chondrocytes. Furthermore, we demonstrated that the transplantation of long-term hypoxic hUC-MSCs (Hy-MSCs) had a better therapeutic effect on OA rats compared with the hUC-MSCs cultured in the normoxic atmosphere (No-MSCs) in terms of the improved function and swelling recovery in the joints, and substantially inhibited the secretion of pro-inflammatory factors, which effectively alleviated cartilage damage by reducing the expression of matrix metallopeptidase 13 (MMP-13). Conclusion. Our results demonstrate that Hy-MSCs possess immense potential for clinical applications via promoting stemness maintenance and enhancing immunoregulatory function. Cite this article: Bone Joint Res 2024;13(12):763–777

Aims: The purpose of this study was to quantify the amount of cell viability and cartilaginous damage present in non-reparable human osteoarticular fragments removed at the time of acetabular fracture surgery. Material and Methods: The cases of 6 patients with comminuted fractures of the acetabulum were prospectively analyzed. Average age was 39 years, and none of them had evidence of preexisting hip pathology. Loose small osteoarticular fragments that were not reparable were microscopically analyzed to assess in-situ cell viability. Observations were divided into (i) depth of chondrocyte death from the articular surface, and (ii) structural matrix damage and cell death under regular histology. The depth of cell death was classiþed as mild between 1 and 15%, moderate from 15 to 30%, severe from 31 to 60% and total from 61 to 100%. Results: Five of the patients were classiþed as having only mild amount of chondrocyte death and one specimen had a moderate amount of chondrocyte death. The articular surface damage was mainly located on the superþcial zone of the cartilage. Discussion and conclusion: Most of the chondrocytes on small osteochondral fragments removed from displaced intraarticular acetabular fractures were still viable after having received a substantial amount of trauma.

Aims. The primary aim of this study was to determine the ten-year outcome following surgical treatment for femoroacetabular impingement (FAI). We assessed whether the evolution of practice from open to arthroscopic techniques influenced outcomes and tested whether any patient, radiological, or surgical factors were associated with outcome. Methods. Prospectively collected data of a consecutive single-surgeon cohort, operated for FAI between January 2005 and January 2015, were retrospectively studied. The cohort comprised 393 hips (365 patients; 71% male (n = 278)), with a mean age of 34.5 years (SD 10.0). Over the study period, techniques evolved from open surgical dislocation (n = 94) to a combined arthroscopy-Hueter technique (HA + Hueter; n = 61) to a pure arthroscopic technique (HA; n = 238). Outcome measures of interest included modes of failures, complications, reoperation, and patient-reported outcome measures (PROMs). Demographic, radiological, and surgical factors were tested for possible association with outcome. Results. At a mean follow-up of 7.5 years (SD 2.5), there were 43 failures in 38 hips (9.7%), with 35 hips (8.9%) having one failure mode, one hip (0.25%) having two failure modes, and two hips (0.5%) having three failure modes. The five- and ten-year hip joint preservation rates were 94.1% (SD 1.2%; 95% confidence interval (CI) 91.8 to 96.4) and 90.4% (SD 1.7%; 95% CI 87.1 to 93.7), respectively. Inferior survivorship was detected in the surgical dislocation group. Age at surgery, Tönnis grade, cartilage damage, and absence of rim-trimming were associated with improved preservation rates. Only Tönnis grade was an independent predictor of hip preservation. All PROMs improved postoperatively. Factors associated with improvement in PROMs included higher lateral centre-edge and α angles, and lower retroversion index and BMI. Conclusion. FAI surgery provides lasting improvement in function and a joint preservation rate of 90.4% at ten years. The evolution of practice was not associated with inferior outcome. Since degree of arthritis is the primary predictor of outcome, improved awareness and screening may lead to prompt intervention and better outcomes. Cite this article: Bone Jt Open 2022;3(10):804–814

Aims. Osteoarthritis (OA) is a common degenerative joint disease characterized by chronic inflammatory articular cartilage degradation. Long noncoding RNAs (lncRNAs) have been previously indicated to play an important role in inflammation-related diseases. Herein, the current study set out to explore the involvement of lncRNA H19 in OA. Methods. Firstly, OA mouse models and interleukin (IL)-1β-induced mouse chondrocytes were established. Expression patterns of IL-38 were determined in the synovial fluid and cartilage tissues from OA patients. Furthermore, the targeting relationship between lncRNA H19, tumour protein p53 (TP53), and IL-38 was determined by means of dual-luciferase reporter gene, chromatin immunoprecipitation, and RNA immunoprecipitation assays. Subsequent to gain- and loss-of-function assays, the levels of cartilage damage and proinflammatory factors were further detected using safranin O-fast green staining and enzyme-linked immunosorbent assay (ELISA) in vivo, respectively, while chondrocyte apoptosis was measured using Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) in vitro. Results. IL-38 was highly expressed in lentivirus vector-mediated OA mice. Meanwhile, injection of exogenous IL-38 to OA mice alleviated the cartilage damage, and reduced the levels of proinflammatory factors and chondrocyte apoptosis. TP53 was responsible for lncRNA H19-mediated upregulation of IL-38. Furthermore, it was found that the anti-inflammatory effects of IL-38 were achieved by its binding with the IL-36 receptor (IL-36R). Overexpression of H19 reduced the expression of inflammatory factors and chondrocyte apoptosis, which was abrogated by knockdown of IL-38 or TP53. Conclusion. Collectively, our findings evidenced that upregulation of lncRNA H19 attenuates inflammation and ameliorates cartilage damage and chondrocyte apoptosis in OA by upregulating TP53, IL-38, and by activating IL-36R. Cite this article: Bone Joint Res 2022;11(8):594–607

Previous studies showed that telo-peptides degraded from type II collagen, a type of collagen fragments, could induce cartilage damage in bovine stifle joints. We aim to investigate the role of integrins (ITGs) and matrix metalloproteinases (MMPs) in collagen fragment-induced human cartilage damage that is usually observed in osteoarthritis (OA). We hypothesized that N-telopeptide (NT) derived from type II collagen could up-regulate the expression of β1 integrin (ITGB1) and then MMPs that may lead to osteoarthritic cartilage damage. Human chondrocytes were isolated from femoral head or tibial plateau of patients receiving arthroplasty (N = 24). Primary chondrocyte cultures were either treated with 30 µM NT, or 30 µM scrambled NT (SN), or PBS, or left untreated for 24 hrs. Total proteins and RNAs were extracted for examination of expression of ITGB1 and MMPs-3&13 with Western blotting and quantitative real-time PCR. Compared to untreated or PBS treated chondrocytes, NT-treated chondrocytes expressed significantly higher levels of ITGB1 and MMPs-3&-13. However, SN also up-regulated expression of ITGB1 and MMP-13. ITGB1 and MMPs-3&-13 might mediate the catalytic effect of NT, a type of collagen fragments, on human cartilage damage that is a hallmark of OA

Although remnant-preserved ACL reconstruction (ACLR) restores knee joint stability and dampens the problem of acute ACL rupture-induced knee pain, an increasing number of patients still develop post-traumatic osteoarthritis (PTOA) after 10 to 15 years of ACLR. We previously found that remnant-preserved ACLR with concomitant medial and lateral meniscus repair may not prevent cartilage degeneration and weaken muscle strength, while the clinical features of PTOA are not clear. We hypothesized that remnant-preserved ACLR with concomitant medial and lateral meniscus tears is related to early cartilage damage, worse function recovery, patient-reported outcomes (PROs) and delayed duration to return to sports. The aim is to evaluate the remnant-preserved ACLR with complicated meniscal injuries in predicting which patients are at higher risk of osteoarthritic changes, worse function and limited activities after ACLR for 12 months. Human ethical issue was approved by a committee from Xi'an Jiaotong University. 26 young and active patients (24 male, 2 female) with ACL injuries (Sherman type I and II) with concomitant medial and lateral meniscus within 2 months were included from January 2014 to March 2022. The average age of the ACLR+ meniscus repair was 26.77±1.52 (8 right, 5 left) and isolated ACLR control was 31.92±2.61 years old (7 left, 6 right). Remnant-preserved ACLR with a 5- to 6-strand hamstring tendon graft was operated on by the same sports medicine specialists. MRI CUBE-T. 2. scanning with 48 channels was conducted by a professional radiologist. The volume of the ACL graft was created through 3 dimensional MRI model (Mimics 19, Ann Arbor). Anterior Cruciate Ligament OsteoArthritis Score (ACLOAS) was applied to score visible cartilage damage. IKDC 2000 score and VAS were assessed by two blinded researchers. Results were presented as mean± SEM of each group. The cross-sectional area and 3D volume of the ACL graft were greater in the remnant-preserved ACLR+meniscus group compared with isolated ACLR (p=0.01). It showed that ACLR+ meniscus group had early signs of joint damage and delayed meniscus healing regarding ACLOAS compared to control group (p=0.045). MRI CUBE-T. 2. prediction of radiographic cartilage degeneration was not obvious in both groups post remnant-preserved ACLR over 12 months (p>0.05). However, higher VAS scores, lower IKDC scores, and long-last joint swelling were reported in the ACLR+ meniscus repair group at the end of 12 months follow-up. Although remnant-preserved ACLR+ meniscus was able to maintain the restore the knee function, it showed delayed timing (>12 months) to return to play at the pre-injury stage, while no difference between the timing of returning to the normal daily routine of their ACLR knee compared to control (p=0.30). The cost of ACLR+ meniscus (average 10,520.76$) was higher than the control group (6,452.92$, p=0.018). Remnants-preserved ACLR with concomitant injured medial and lateral meniscus repair shows a higher risk of cartilage damage, greater cost, worse functional performance, and longer time for young male patients to return to sports after 12-month follow-up compared to isolated ACLR. Further evidence and long-term follow-up are needed to better understand the association between these results and the risk of development of PTOA in this patient cohort

Abstract. Introduction. The outcome of revision anterior cruciate ligament reconstruction (ACL-R) is guarded, particularly their return to sports activities. It is important to know the factors affecting the functional outcomes following a revision ACL-R. Methods. We analysed results from 39 patients, who underwent a revision ACL reconstruction by a single surgeon and was followed up over a year. Some of them were treated in 2-stage revision while the rest were single-stage revision, depending upon their size of bone tunnel or osteolysis as assessed by pre-operative CT scan. Result. We analysed data from 39 patients with a mean age of 31 (17–52) and an average follow-up of 3.6 years (2–5 years). The average KOOS quality of life score was 58.94 (±23.02) and the mean Lysholm score was 89.48 (±10.1). Medial meniscal tear was significantly correlated with Lysholm score (p<0.005), but not with KOOS-QOL. Tear in lateral meniscus was not related significantly. Patients having Grade II or above cartilage damage showed inferior outcomes in terms of Lysholm score and poor return to sports, and it was statistically significant (p<0.02). There was no significant differences in outcomes between single stage revision and 2-stage revision (p=0.336). 15 patients (42.5%) returned to their pre-injury sports activities after revision surgery with the mean return to sports score of 58.65 (±16.1). Conclusions. The long-term functional outcome after revision ACL reconstruction is satisfactory, but not the return to sports. Expectations on outcome should be carefully managed particularly those having concomitant medial meniscal injury or cartilage damage

Objectives. Articular cartilage damage is a primary outcome of pre-clinical and clinical studies evaluating meniscal and cartilage repair or replacement techniques. Recent studies have quantitatively characterized India Ink stained cartilage damage through light reflectance and the application of local or global thresholds. We develop a method for the quantitative characterisation of inked cartilage damage with improved generalisation capability, and compare its performance to the threshold-based baseline approach against gold standard labels. Methods. The Trainable WEKA Segmentation (TWS) tool (Arganda-Carreras et al., 2017) available in Fiji (Rueden et al., 2017) was used to train two separate Random Forest classifiers to automatically segment cartilage damage on ink stained cadaveric ovine stifle joints. Gold standard labels were manually annotated for the training, validation and test datasets for each of the femoral and tibial classifiers. Each dataset included a sample of medial and lateral femoral condyles and tibial plateaus from various stifle joints, selected to ensure no overlap across datasets according to ovine identifier. Training was performed on the training data with the TWS tool using edge, texture and noise reduction filters selected for their suitability and performance. The two trained classifiers were then applied to the validation data to output damage probability maps, on which a threshold value was calibrated. Model predictions on the unseen test set were evaluated against the gold standard labels using the Dice Similarity Coefficient (DSC) – an overlap-based metric, and compared with results for the baseline global threshold approach applied in Fiji as shown in Figures 1 and 2. Results. Test set results for the global threshold approach against gold standard labels were 45.0% DSC for the femoral condyle and 32.0% DSC for the tibial plateau. Results for the developed TWS classifiers on the same unseen test data were 79.0% and 72.7% DSC, showing absolute gains of 34.0% and 40.7% DSC over the global threshold baseline for the femoral and tibial classifiers. The trained TWS classifiers were then applied to an external set of unlabelled images of ink stained femoral condyles and tibial plateaus. Model results on sample images shown in Figure 3 further highlight the generalisation capability of the developed models. The most prominent classification features were Hessian filters (32.9%), Entropy (19.4%), Gaussian blur (10.1%), Gabor filters (6.3%) and Sobel filters (6.0%), with all other features contributing less than 6%. Conclusions. Our findings show that the developed segmentation method more accurately quantifies cartilage damage and provides improved generalisation capability over a range of input variations such as inconsistent orientation and lighting conditions. The developed model enables the use of articular cartilage damage as a reliable and quantitative outcome measure in studies involving large datasets, with reduced requirements for complex pre-processing and specialised equipment. For any figures or tables, please contact the authors directly

Aims. Osteoarthritis (OA) is a prevalent joint disorder with inflammatory response and cartilage deterioration as its main features. Dihydrocaffeic acid (DHCA), a bioactive component extracted from natural plant (gynura bicolor), has demonstrated anti-inflammatory properties in various diseases. We aimed to explore the chondroprotective effect of DHCA on OA and its potential mechanism. Methods. In vitro, interleukin-1 beta (IL-1β) was used to establish the mice OA chondrocytes. Cell counting kit-8 evaluated chondrocyte viability. Western blotting analyzed the expression levels of collagen II, aggrecan, SOX9, inducible nitric oxide synthase (iNOS), IL-6, matrix metalloproteinases (MMPs: MMP1, MMP3, and MMP13), and signalling molecules associated with nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Immunofluorescence analysis assessed the expression of aggrecan, collagen II, MMP13, and p-P65. In vivo, a destabilized medial meniscus (DMM) surgery was used to induce mice OA knee joints. After injection of DHCA or a vehicle into the injured joints, histological staining gauged the severity of cartilage damage. Results. DHCA prevented iNOS and IL-6 from being upregulated by IL-1β. Moreover, the IL-1β-induced upregulation of MMPs could be inhibited by DHCA. Additionally, the administration of DHCA counteracted IL-1β-induced downregulation of aggrecan, collagen II, and SOX9. DHCA protected articular cartilage by blocking the NF-κB and MAPK pathways. Furthermore, DHCA mitigated the destruction of articular cartilage in vivo. Conclusion. We present evidence that DHCA alleviates inflammation and cartilage degradation in OA chondrocytes via suppressing the NF-κB and MAPK pathways, indicating that DHCA may be a potential agent for OA treatment. Cite this article: Bone Joint Res 2023;12(4):259–273

Abstract. BACKGROUND. Hemi-arthroplasty (HA) as a treatment for fractured neck of femur has slightly increased since 2019 and remarkably after the COVID pandemic. The main drawback of the treatment is ongoing cartilage deterioration that may require revision to THR. OBJECTIVE. This study assessed cartilage surface damage in hip HA by reproducing anatomical motion and loading conditions in a hip simulator. METHODS. Experimental design. HA tests were conducted using porcine acetabula and CoCr femoral heads. Five groups (n=4) were included: a control group comprising natural tissue and four HA groups where the acetabula were paired with metal heads to allow radial clearance (RC) classed as small (RC<0.6mm), large (2mm<RC<4mm), extra-large (4mm<RC), and oversized (RC<−0.6mm). Tests were carried out in an anatomical hip simulator that reproduced a simplified twin peak gait cycle, adapted for porcine hip joints, from the ISO 14242 standard for wear of THR prostheses (peak load of 900N). The test length was 6 hours, with photogrammetry taken at 1-hour intervals. Ringers solution was used as a lubricant. RESULTS. No changes were observed in the control group. However, cartilage surface changes were observed in all hemi-arthroplasty groups. Discolouration on the cartilage surface was noticeable at the posterior-superior part of the acetabulum after 1-hour (extra-large and oversized groups). Damage severity and location were characteristic of each clearance group. Of all the groups, the oversized group showed more significant damage. No labrum separation was seen after the simulation. CONCLUSIONS. These results are relevant to understand the effect of femoral head clearance on cartilage damage risk after HA. Declaration of Interest. (a) fully declare any financial or other potential conflict of interest

Osteoarthritis (OA) is the most common joint disease, affecting approximately 16% of the adult population worldwide. The chronic inflammation in the joint leads to the breakdown of cartilage, which leads to permanent pain and limitations in everyday life at an early stage of the disease. To date, there is no therapy that can interrupt the inflammatory state or reverse cartilage damage. The PROTO consortium (funded by the EU Horizon Europe program, Grant 101095635) aims to prevent the development of OA by correcting a pathological biomechanical pattern by a digital training intervention and to treat early stage OA with an innovative allogeneic cell therapy

Knee arthroscopy is typically approached from the anterior, posteromedial and posterolateral portals. Access to the posterior compartments through these portals can cause iatrogenic cartilage damage and create difficulties in viewing the structures of the posterior compartments. The purpose of this study was to assess the feasibility of needle arthroscopy using direct posterior portals as both working and visualising portals. For workability, the needle scope was inserted advanced from anterior between the cruciate ligament bundle and the lateral wall of the medial femoral condyle until the posterior compartments were visualised. For visualisation, direct postero-lateral and -medial portals were established. The technique was performed in 9 knees by two experienced researchers. Workability and instrumentation of the posteromedial compartment and meniscus was achieved in 56%. The posterior horns could not be visualised in four specimens as the straight lens could not provide a more medial field of view. Visualisation from the direct medial posterior portal allowed a clear view of the medial meniscus, femoral condyle and posterior cruciate ligament in all specimens. Workability and instrumentation of the posterolateral compartment was not possible with the needle scope. Direct posterior approaches for the posteromedial compartment access are challenging with the current needle scope options and could only be achieved in over 50%. The postero-lateral compartment was not accessible. An angled lens or a flexible Needle scope would be better suited for developing this technique further

Osteoarthritis (OA) is the leading cause of pain and disability worldwide and is characterized by the degenerative changes of articular cartilage. Joint loading is required for cartilage maintenance; however, hyper-physiologic loading is a risk factor for OA. Mechanosensitive ion channels Piezo1 and Piezo2 synergistically transduce hyper-physiologic compression of chondrocytes, leading to chondrocyte death and onset of OA. This injury response is inhibited by Piezo channel loss of function, however the mechanistic role of Piezo channels in vivo is unknown. We examined the hypothesis that deletion of Piezo in chondrocytes will protect mice from joint damage and pain-related behaviors following a surgical destabilization of the medial meniscus (DMM), investigating a key mechanistic and mechanobiological role of these channels in the pathogenesis of OA. Aggrecan-Cre Piezo1 and Piezo1/2 knockout mice ((Agc)1-CRE. ERT2. ;Piezo1. fl/fl. Piezo2. fl/fl. ) were generated and given a 5-day Tamoxifen regimen at 12-weeks of age (n=6–12/group/sex). Cre-negative mice served as controls. At 16-weeks, mice received DMM surgery on the left knee. 12-weeks following DMM prior to sacrifice, activity and hyperalgesia were measured using spontaneous running wheels and a small animal algometer. Structural changes in bone, cartilage, and synovium were characterized using microCT, histology, and Modified Mankin Score criteria. Knockout of Piezo1/2 channels was chondroprotective in both sexes following DMM surgery as demonstrated by reduced Modified Mankin Score compared to control animals. Piezo1 KO was chondroprotective in only female mice, indicating a sexually dimorphic response. Piezo1 and Piezo1/2 KO was protective against pain in male mice, while females displayed no differences compared to controls. No changes were observed in bone morphology. Chondrocyte-specific Piezo1/2 knockout protects the knee joint from structural damage, hyperalgesia and functional deficits in a surgical model of PTOA in male and female mice, illustrating the importance of Piezo channels in response to injury in vivo. Future work aims to interrogate potential sexually dimorphic responses to cartilage damage and investigating Piezo2 KO mice

Introduction. Cartilage damage is a critical aspect of osteoarthritis progression, but effective imaging strategies remain limited. Consequently, multimodal imaging approaches are receiving increased attention. Gold nanomaterials, renowned for their therapeutic and imaging capabilities, hold promise in drug development. However, their potential for cartilage imaging is rarely discussed. Here, we developed a versatile nanomaterial, AuNC@BSA-Gd-I, for cartilage detection. By leveraging electrostatic interactions with sulfated glycosaminoglycans (sGAG), the AuNC@BSA-Gd-I can effectively penetrate damaged cartilage while accumulating minimally in healthy cartilage. This probe can be visualized or detected using CT, MRI, IVIS, and a gamma counter, providing a comprehensive approach to cartilage imaging. Additionally, we compared the imaging abilities, cartilage visualization capacities, and versatility of currently disclosed multimodal gold nanomaterials with those of AuNC@BSA-Gd-I. Method. The physicochemical properties of nanomaterials were measured. The potential for cartilage visualization of these nanomaterials was assessed using an in vitro porcine model. The sGAG content in cartilage was determined using the dimethylmethylene blue (DMMB) assay to establish the correlation between sGAG concentration and imaging intensity acquired at each modality. Results. The cartilage imaging abilities of AuNC@BSA-Gd-I for CT, MRI, and optical imaging were verified, with each imaging intensity demonstrating a strong correlation with the sGAG content (MRI; R2=0.93, CT; R2=0.83, IVIS; R2=0.79). Furthermore, AuNC@BSA-Gd-. 131. I effectively accumulated in defective cartilage tissue compared to healthy cartilage (23755.38 ± 5993.61 CPM/mg vs. 11699.97 ± 794.93 CPM/mg). Additionally, current gold nanomaterials excelled in individual imaging modalities but lacked effective multimodal imaging ability. Conclusion. Compared to current multimodal gold nanomaterials, AuNC@BSA-Gd-I demonstrates the potential to image cartilage across multiple medical instruments, providing investigators with a more powerful, visible, and convenient approach to detect cartilage defects. Acknowledgements. This work was financially supported by the National Health Research Institute, Taiwan (NHRI-EX112-11029SI), the National Science and Technology Council (NSTC 112-2314-B-182A-105-MY3), and Chang Gung Memorial Hospital, Taiwan (CMRPG8N0781 and CMRPG8M1281-3)