Introduction. The presence of pluripotent mesenchymal cells in the periosteum along with the growth factors produced or released following injury provides this tissue with an important role in bone healing. Utilising this property, vascularised periosteal flaps may increase the union rates in recalcitrant atrophic long bone non-union. The novel chimeric fibula-periosteal flap utilises the periosteum raised on an independent periosteal vessel, thus allowing the periosteum to be inset freely around the osteotomy site, improving bone
Tendon healing is a complex process that often results in compromised healing of the tendon tissue. It has recently been shown that temporal changes in the expression profile and the histological tissue quality of the tendons occur during the early healing process after acute Achilles tendon rupture. Whether these changes are accompanied by an altered healing process, is not yet known and was the aim of the present study. Tendon biopsies were obtained from 24 patients with acute Achilles tendon rupture at the time of surgery (2–9 days after rupture) and examined histologically as well as on RNA level. Histologically, the tendon architecture, the amount of aligned collagen, glycosaminoglycan and fat as well as the cellularity, vascularity and immune cell infiltration were determined. On RNA level the expression of markers for the modeling/remodeling (MMPs and TIMPs), collagens (1, 3, 5), tendon markers (scleraxis, tenomodulin), pro- and anti-inflammatory markers (IL-1beta, IL6, IL10, IL33, TNFa, TGF-beta1, COX2) and immune cell markers (CD3, CD68, CD80, CD206) were analyzed by Real-Time PCR. To determine the clinical outcome, the patients were followed up 12 months after the operation and the following scores were recorded: Subjective score, Tegner score, Visual Analog Scale (VAS) pain, VAS function, Matles Test, Achilles tendon total rupture score (ATRS), Therman 100-points score, Heel rise test. Statistics: Spearman correlation analysis. Correlation analysis shows that early post-rupture surgery is associated with better clinical outcome (ATRS Score: p=0.022). Histologically, a good functional healing outcome shows a positive correlation to the amount of aligned collagen (Heel Rise Test: p = 0.009) and glycosaminoglycans in the tendon (Heel Rise Test: p = 0.026, Matles difference: p = 0.029), as well as a negative correlation to the fat content (Thermann score: p = 0.018, subjective score: p = 0.027, VAS function: p = 0.031). On RNA level, a good healing outcome correlates with increased expression of MMP13, collagen 1, 3, 5 (Heel Rise Test: p = 0.019, p = 0.048, p = 0.030), and TIMP2 (Tegner Score: p = 0.040), TGF-beta1 (Thermann Score: p = 0.032) and CD80 (ATRS: p = 0.025, Thermann score:, p = 0.032). Whereas a limited healing outcome is associated with an increased expression of MMP2 (Heel Rise Test: p = 0.033), MMP3 (Matles Test: p=0.001, Heal Rise test p = 0.017), and IL33 (Tegner Score: p = 0.047). The results of the study show a clear relationship between the tendon
Remodeling of the cancellous bone is more active than that of the cortical bone. It is known that the remodeling is governed by the intracancellous fluid pressure. Particularly, the lacunocanalicular pore (PLC) fluid pressure (FP) is essential for survival of the osteocyte and communication of remodeling signals between the PLC and intertrabecular pore (PIT). As a result, knowledge about the PLCFP generation of trabeculae is required to understand human cancellous bone
Impaired bone healing
Impaired bone healing
Aims: Identifying low-grade infection in failed total hip replacements (THR) is an important but often difficult task. Recently, there has been interest in the use of molecular
Surgical reconstruction of the injured Anterior Cruciate Ligament (ACL) is an effective solution to knee instability, but not all grafts incorporate well. The biological environment in the knee that controls graft integration is not well understood, and this study aims to fill that gap as the first step towards a translational approach to optimise outcomes. Over two stages, tissue samples and knee fluid samples were harvested from patients undergoing ACL reconstruction. These samples were cultured and stored to allow batch analysis for a variety of cytokines, growth factors and collagenases. Stage 1 (n=14) identified the presence of specific pro-inflammatory cytokines, growth factors and latent collagenase. Information gathered allowed a more targeted approach to be used in stage 2 (n=18). Stage 2 data from tissue cultures suggest that collagenase activity peaks later than 6 hours post-op. The relationships between collagenase activity and levels of TNF-alpha, IL-1beta and bFGF are of potential interest, and the profiles of patients will be compared with longer term follow-up data to determine any effects on outcomes. Further detailed assessment of the
The establishment of a proper musculoskeletal system depends on the well-organized and synchronized development of muscle, tendon and cartilage/bone. In tendon
Osteosarcoma despite considerable biological and molecular heterogeneity, being defined by a phenotypic program resulting in the production of osteoid, is a relatively consistent clinical entity. Over the past 20 years a large catalogue of genetic alterations present in osteosarcoma has been compiled, but unfortunately this information has yielded little biological understanding or widely accepted prognostic factor. In an analogous manner nearly two decades of clinical trials, most incorporating new agents or intensifying therapy have not further improved the prognosis of patients with osteosarcoma. This would lead to considerable pessimism if it were not for the dramatic expansion in availability of osteosarcoma models, tissues resources as well as new agents, particularly antibodies targeted to various cell surface receptor proteins. Selecting and applying these agents will require an understanding of osteosarcoma’s unique dependencies and may also have the potential to yield biological insights. Defining these dependencies has been complicated by osteosarcoma’s genetic complexity as well as redundant expression of cell surface receptors, but efficacy of antibody-based targeted therapies may assist in defining the relative importance of receptors as well as their downstream signal transduction pathways. The availability of these new tissue resources and murine models may assist in understanding osteosarcoma’s complex
In developed nations Charcot arthropathy is most commonly caused by diabetes mellitus. Worldwide, leprosy remains the primary cause. All evidence points to a relationship between neurologic loss, continued loading activities and the development of unrecognized bone fragmentation. In type 2 diabetes, dysregulation of leptin
Massive uncontained glenoid defects are a difficult surgical problem requiring reconstruction in the setting of either primary or revision total shoulder arthroplasty. Our aim is to present a new one-stage technique that has been developed in our institution for glenoid reconstruction in the setting of massive uncontained glenoid bone loss. We utilise a modified delto-pectoral approach to perform our dual
Summary Statement. Dickkopf-3 is upregulated in OA cartilage and synovial tissue. In vitro studies show Dkk3 can prevent cartilage degradation and antagonise Wnt signaling. We hypothesis that Dkk3 can protect against OA-related cartilage destruction. Introduction. Our group has previously shown that Dkk3, a member of the Dkk family of Wnt antagonists, is upregulated in OA cartilage and synovium. Levels of Dkk3 in synovial fluid are also increased in individuals with tricompartmental OA and after arthroscopy. The role of Dkk3 in cartilage or the factors regulating its expression are not currently understood. Correct regulation of cell signalling pathways is integral to cartilage homeostasis and thus the prevention of OA pathogenesis. Dkk3 is a member of the Dkk family of Wnt antagonists and therefore may impact on chondrocyte
Intervertebral disc degeneration has been associated with low back pain (LBP) which is a major cause of long-term disability worldwide. Observed mechanical and biological modifications have been related to decreased water content. Clinical traction protocols as part of LBP management have shown positive outcomes. However, the underlying mechanical and biological processes are still unknown. The study purpose was to evaluate the impact of unloading through traction on the mechanobiology of healthy bovine tail discs in culture. We loaded bovine tail discs (n=3/group) 2h/day at 0.2Hz for 3 days, either in dynamic compression (-0.01MPa to -0.2MPa) or in dynamic traction (-0.01MPa to 0.024MPa). In between the dynamic loading sessions, we subjected the discs to static compression loading (-0.048MPa). We assessed biomechanical and biological parameters.Introduction
Method
Cigarette smoking has a negative impact on the skeletal system by reducing bone mass and increasing the risk of fractures through its direct or indirect effects on bone remodeling. Recent evidence shows that smoking causes an imbalance in bone turnover, making bone vulnerable to osteoporosis and fragility fractures. In addition, cigarette smoking is known to have deleterious effects on fracture healing, as a positive correlation has been shown between the daily number of cigarettes smoked and years of exposure to smoking, although the underlying mechanisms are not fully understood. Smoking is also known to cause several medical and surgical complications responsible for longer hospital stays and a consequent increase in resource consumption. Smoking cessation is, therefore, highly advisable to prevent the onset of metabolic bone disease. However, some of the consequences appear to continue for decades. Based on this evidence, the aim of our work was to assess the impact of smoking on the skeletal system, particularly bone fractures, and to identify the pathophysiological mechanisms responsible for the impairment of fracture healing. Because smoking represents a major public health problem, understanding the association between cigarette smoking and the occurrence of bone disease is necessary in order to identify potential new targets for intervention.
RNA-Seq or whole transcriptome shotgun sequencing has been adopted in the last years as a reference technique to determine the presence and the quantity of different species of RNA in determined biological samples, thanks to it allows the identification every single RNA species transcribed from a reference genome. Meta-profiling takes advantage of the public availability of an increasing set of RNA-Seq data produced by different laboratories to summarize the expression levels of the different RNA species of many samples according to their biological context, giving the opportunity to perform comparisons on the gene expression profiles of different tissues by integrating data derived from a high number of studies. By using Genevestigator™; a platform which integrates RNA-Seq data into meta-profiles, we have performed a comparison between the gene expression profiles of bone, cartilage, muscle tendon and skin by means of interrogating its database with different gene sets and families with relevance to the function of the tissues of the musculoskeletal system. The collagen gene family and genes coding for proteoglycans, matrix metalloproteinases and tissue inhibitors of metalloproteinases, mechanotransduction-related proteins and signalling pathways involved in tissue development and differentiation have been analysed. Hierarchical clustering for every gene set was performed for the understanding the differences and similarities between the different tissues included in the analyses. The results of this study will help to improve our understanding of the musculoskeletal system, and will help to identify new biomarkers and signalling pathways of specific relevance for the bone, cartilage, muscle and tendon.
In cementless fixation system, surface character becomes important factor. Alkali and heat treatments on titanium metal has been proved to show strong bonding to bone and higher ongrowth rate. In this study we examined the effect of alkali and heat treatments on titanium rod in rabbit femur intramedurally model, in consideration of cementless hip stem. The implant had a 5mm in diameter and 25 mm in length. The implants were and half of them were immersed in 5 mol/L sodium hydroxide solution and heated at 600 åé for one hour (AH implant), and the other half were untreated (CL implant). The implants were implanted into the distal femur of the rabbits, AH implant into left femur and CL implants into right. The bone-implant interfaces were evaluated at 3, 6, and 12 weeks after implantations. Pull-out tests showed that AH implants significantly higher bonding strength to bone than CL implants at each week after operations. At 12 weeks mean pull-out load of AH implants was 411.7 N and that of CL implants 72.2 N. As postoperative time elapsed, histological examination revealed that new bone form on the surface of the both types of the implants, but significantly more bone contacted directly on the surface of AH implants. At 12 weeks AH implant was covered by the newly formed bone about 56% of the whole surface of the implants and CL implants was about 19%. In conclusion, alkali- and heat-treated titanium offers strong bone-bonding and high affinity to bone instead of conventional mechanical interlocking mechanism. Alkali and heat treatments on titanium may be applicable to the surface treatment for cementless joint replacement implant.