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. 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.Aims
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Osteonecrosis of the femoral head after femoral neck fracture (ONFHpoFNFx) poses challenges in children, particularly at Ficat III stage. Limited effective treatments are available. This study explores basicervical femoral neck rotational osteotomy (BFNRO) for ONFHpoFNFx in children and adolescents and evaluates its outcomes. Children and adolescents with ONFHpoFNFx (Ficat stage III) underwent BFNRO at our center from June 2017 to September 2022 were included. Follow-up exceeded 1 year, with data on modified-Harris-hip-score (mHHS), range of motion (ROM), patient satisfaction, femoral head collapse, necrotic area repair, leg-length, and osteoarthritis progression recorded. This study included 15 cases (15 hips), with 8 males and 7 females, averaging 12.9 years in age (range: 10–17 years). Nine cases had BFNRO alone, and six had combined PAO. Rotation angles varied from 70° to 90° for anterior rotation and 110° to 135° for posterior rotation. Nine patients had femoral neck fixation in a varus position (10° to 30°). The postoperative contour of the weight-bearing area of the femoral head has significantly improved in all patients. With an average follow-up of 28.6 months (range: 12.2–72.7 months), mHHS significantly improved (65.2 to 90.2, P<0.001). Only one patient showed femoral head collapse. Patients experienced no/mild hip pain (VAS=0-3), slight restriction in range of motion, and mild limb shortening. Two patients showed osteoarthritis progression. No infections, joint replacements, or nerve injuries were observed. Even in cases of ONFHpoFNFx in the late stage, BFNRO in children and adolescents can still yield positive early to mid-term results by relocating the necrotic area and restoring the integrity of the anterior-lateral column of the femoral head, thereby preventing femoral head collapse and delaying the onset of severe osteoarthritis.
To explore the clinical efficacy of using two different types of articulating spacers in two-stage revision for chronic knee periprosthetic joint infection (kPJI). A retrospective cohort study of 50 chronic kPJI patients treated with two types of articulating spacers between January 2014 and March 2022 was conducted. The clinical outcomes and functional status of the different articulating spacers were compared. Overall, 17 patients were treated with prosthetic spacers (prosthetic group (PG)), and 33 patients were treated with cement spacers (cement group (CG)). The CG had a longer mean follow-up period (46.67 months (SD 26.61)) than the PG (24.82 months (SD 16.46); p = 0.001).Aims
Methods
Stem cell therapy is an effective means to address the repair of large segmental bone defects. However, the intense inflammatory response triggered by the implants severely impairs stem cell differentiation and tissue regeneration. High-dose transforming growth factor β1 (TGF-β1), the most locally expressed cytokine in implants, inhibits osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and promotes tissue fibrosis, severely compromising the efficacy of stem cell therapy. Small molecule inhibitors of TGF-β1 can be used to ameliorate the osteogenic disorders caused by high concentrations of TGF-β1, but systemic inhibition of TGF-β1 function will cause strong adverse effects. How to find safe and reliable molecular targets to antagonize TGF-β1 remains to be elucidated. Orphan nuclear receptor Nr4a1, an endogenous inhibitory molecule of TGF-β1, suppresses tissue fibrosis, but its role in BMSC osteogenesis is unclear. We found that TGF-β1 inhibited Nr4a1 expression through HDAC4. Overexpression of Nr4a1 in BMSCs reversed osteogenic differentiation inhibited by high levels of TGF- β1. Mechanistically, RNA sequencing showed that Nr4a1 activated the ECM-receptor interaction and Hippo signaling pathway, which in turn promoted BMSC osteogenesis. In bone defect repair and fracture healing models, transplantation of Nr4a1-overexpressing BMSCs into C57BL/6J mice or treatment with the Nr4a1 agonist Csn-B significantly ameliorated inflammation-induced bone regeneration disorders. In summary, our findings confirm the endogenous inhibitory effect of Nr4a1 on TGF- β1 and uncover the effectiveness of Nr4a1 agonists as a therapeutic tool to improve bone regeneration, which provides a new solution strategy for the treatment of clinical bone defects and inflammatory skeletal diseases.
Mendelian randomization (MR) is considered to overcome the bias of observational studies, but there is no current meta-analysis of MR studies on rheumatoid arthritis (RA). The purpose of this study was to summarize the relationship between potential pathogenic factors and RA risk based on existing MR studies. PubMed, Web of Science, and Embase were searched for MR studies on influencing factors in relation to RA up to October 2022. Meta-analyses of MR studies assessing correlations between various potential pathogenic factors and RA were conducted. Random-effect and fixed-effect models were used to synthesize the odds ratios of various pathogenic factors and RA. The quality of the study was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology using Mendelian Randomization (STROBE-MR) guidelines.Aims
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This study aimed to investigate the role and mechanism of meniscal cell lysate (MCL) in fibroblast-like synoviocytes (FLSs) and osteoarthritis (OA). Meniscus and synovial tissue were collected from 14 patients with and without OA. MCL and FLS proteins were extracted and analyzed by liquid chromatography‒mass spectrometry (LC‒MS). The roles of MCL and adenine nucleotide translocase 3 (ANT3) in FLSs were examined by enzyme-linked immunosorbent assay (ELISA), flow cytometry, immunofluorescence, and transmission electron microscopy. Histological analysis was performed to determine ANT3 expression levels in a male mouse model.Aims
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Eccentric reductions may become concentric through femoral head ‘docking’ (FHD) following closed reduction (CR) for developmental dysplasia of the hip (DDH). However, changes regarding position and morphology through FHD are not well understood. We aimed to assess these changes using serial MRI. We reviewed 103 patients with DDH successfully treated by CR and spica casting in a single institution between January 2016 and December 2020. MRI was routinely performed immediately after CR and at the end of each cast. Using MRI, we described the labrum-acetabular cartilage complex (LACC) morphology, and measured the femoral head to triradiate cartilage distance (FTD) on the midcoronal section. A total of 13 hips with initial complete reduction (i.e. FTD < 1 mm) and ten hips with incomplete MRI follow-up were excluded. A total of 86 patients (92 hips) with a FTD > 1 mm were included in the analysis.Aims
Methods
This study aimed to evaluate calprotectin in synovial fluid for diagnosing chronic prosthetic joint infection (PJI) . A total of 63 patients who were suspected of PJI were enrolled. The synovial fluid calprotectin was tested by an enzyme-linked immunosorbent assay (ELISA). Laboratory test data, such as ESR, CRP, synovial fluid white blood cells (SF-WBCs), and synovial fluid polymorphonuclear cells (SF-PMNs), were documented. Chi-squared tests were used to compare the sensitivity and specificity of calprotectin and laboratory tests. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was calculated to determine diagnostic efficacy.Aims
Methods
Femoroacetabular impingement (FAI) is a potential cause of hip osteoarthritis (OA). The purpose of this study was to investigate the expression profile of matrix metalloproteinases (MMPs) in the labral tissue with FAI pathology. In this study, labral tissues were collected from four FAI patients arthroscopically and from three normal hips of deceased donors. Proteins extracted from the FAI and normal labrums were separately applied for MMP array to screen the expression of seven MMPs and three tissue inhibitors of metalloproteinases (TIMPs). The expression of individual MMPs and TIMPs was quantified by densitometry and compared between the FAI and normal labral groups. The expression of selected MMPs and TIMPs was validated and localized in the labrum with immunohistochemistry.Aims
Methods
Chondrocyte hypertrophy represents a crucial turning point during endochondral bone development. This process is tightly regulated by various factors, constituting a regulatory network that maintains normal bone development. Histone deacetylase 4 (HDAC4) is the most well-characterized member of the HDAC class IIa family and participates in different signalling networks during development in various tissues by promoting chromatin condensation and transcriptional repression. Studies have reported that HDAC4-null mice display premature ossification of developing bones due to ectopic and early-onset chondrocyte hypertrophy. Overexpression of HDAC4 in proliferating chondrocytes inhibits hypertrophy and ossification of developing bones, which suggests that HDAC4, as a negative regulator, is involved in the network regulating chondrocyte hypertrophy. Overall, HDAC4 plays a key role during bone development and disease. Thus, understanding the role of HDAC4 during chondrocyte hypertrophy and endochondral bone formation and its features regarding the structure, function, and regulation of this process will not only provide new insight into the mechanisms by which HDAC4 is involved in chondrocyte hypertrophy and endochondral bone development, but will also create a platform for developing a therapeutic strategy for related diseases.
The coronal plane lower limb alignment plays an important role in the occurrence and progression in knee osteoarthritis. There have been reports of the valgus knee in patients with unilateral developmental hip dislocation (UDHD) with the relatively small sample size. Besides, few studies have analyzed the lower limb alignment of the contralateral side. The purpose of our study was to identify the coronal plane alignment of both the ipsilateral and the contralateral lower limb in patients with UDHD and find out the difference between patients with Hartofilakidis type II and III. The radiographic data of all UDHD patients who met the inclusion criteria from March 2011 to February 2017 were retrospectively reviewed, including the hip-knee-ankle angle (HKA), mechanical lateral distal femoral angle (mLDFA), anatomical lateral distal femoral angle (aLDFA), mechanical proximal tibial angle (MPTA) and the lateral distal tibial angle (LDTA). Besides, the femoral torsion angle was measured on the images of CT scan. The average HKA was 3.42°(range: −4.3–12.8°) on the affected side, and −2.11°(range: −11.4–5.4°) on the contralateral side (P?0.0001). The valgus lower limb alignment on ipsilateral side was most frequently seen in both Hartofilakidis type II (20cases, 51.3%) and type III groups (25cases, 67.6%), whereas for the contralateral side, the neutral alignment in type II group (27 cases, 69.2%) and varus alignment in type III group (19 cases, 51.4%) were most commonly observed. Both the mLDFA (P?0.001) and aLDFA (P?0.001) of ipsilateral side were significantly smaller than those of contralateral side. The average femoral torsion angle was 37.9°(range: 10.4–64.4°) on the affected side, and 27.1°(range: 9.7–45.5°) on the contralateral side (P?0.001). In conclusion, UDHD patients may present with lower limb malalignment on both sides. The valgus lower limb alignment is the most common deformity on ipsilateral side, which is caused by increased femoral torsion angle as well as the decreased aLDFA. The patients with Hartofilakidis type III UDHD may be more prone to present varus alignment deformity than those with Hartofilakidis type II on the contralateral side. The lower limb malalignment and deformity of ipsilateral distal femur should be considered during any surgery involving hip, knee or femur.
There is great interest in technologies to improve the accuracy and precision in placing implants for total hip arthroplasty (THA). Malik et al. (J Arthroplasty, 2010) showed that an imageless navigation system could be used to produce accurate measures of acetabular cup alignment compared to a CT-based alignment method using an imaging phantom. In this study we sought to compare the precision of an image-based navigation system with post-operative CT scans in a clinical patient cohort who received navigation-assisted THA. Eighteen patients with 20 hips consented to this IRB-approved analysis of intra- and post-operative THA cup alignment. All patients received THA with image-assisted alignment (MAKO Surgical, Fort Lauderdale). Nominal cup placement, subject to intraoperative surgeon adjustment and approval, was 40° radiographic inclination (RI) and 20° radiographic anteversion (RA) according to the definitions of Murray (JBJS-Br, 1993). Intraoperative cup alignment was measured by collecting five points on the cup rim with an optically tracked stylus. Postoperative cup alignment was measured by registering pre- and post-operative pelvic models generated from CT scans, and determining the postoperative cup orientation relative to the pre-operative pelvis coordinate system (Figure 1). Repeated measures testing of the CT-based measurements on 10 patient scans showed precision and bias of 0.7° and 0° for radiographic inclination, and 0.6° and 0.1° for radiographic anteversion.Introduction
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