Osteoarthritis (OA), the most prevalent chronic joint disease, increases in prevalence with age, and affects majority of individuals over the age of 65 and is a leading musculoskeletal cause of impaired mobility in the elderly. Because the precise molecular mechanisms which are involved in the degradation of cartilage matrix and development of OA are poorly understood and there are currently no effective interventions to decelerate the progression of OA or retard the irreversible degradation of cartilage except for total joint replacement surgery. In this paper, the important molecular mechanisms related to OA pathogenesis will be summarized and new insights into potential molecular targets for the prevention and treatment of OA will be provided.

Objective To determine the benefits of combination treatment with mechanical support and targeted intra-arterial infusion of peripheral blood stem cells (PBSCs) mobilized by granulocyte-colony stimulating factor (G-CSF) via the medial circumflex femoral artery on the progression of osteonecrosis of the femoral head (ONFH). Methods 55 patients (89 hips) with early and intermediate stage ONFH were recruited and randomly assigned to combination treatment or mechanical support treatment (control group). All hips received mechanical support treatment (porous tantalum rod implantation). Then, Hips in the combination treatment group were performed targeted intra-arterial infusion of PBSCs. At each follow-up, Harris hip score (HHS) and Association Research Circulation Osseous classification (ARCO) were used to evaluate the symptoms and progression of osteonecrosis. Total hip arthroplasty (THA) was assessed as an endpoint at each follow-up. Results At 36 months, 9 of the 41 hips (21.95%) in the control group progressed to clinical failure and underwent THA whereas only 3 of the 48 hips (6.25%) in the combination treatment group required THA(p=0.031). Kaplan-Meier survival analysis showed a significant difference in the survival time between the two groups (Log-rank test; p=0.025). Compared to the control group, combination treatment significantly improved the HHS at 36 months (p=0.003). At the final follow-up examination, radiological progression was noted in 13 of 41 hips (31.71%) for the control group, while only in 4 of 48 hips (8.33%) for the combination treatment group (p=0.005). The overall collapse rates were 15.15% (5 of 33 hips) and 8.11% (3 of 37 hips) in the control and combination treatment groups, respectively. Conclusions Targeted intra-arterial infusion of PBSCs is capable of enhancing the efficacy of biomechanical support in the treatment of ONFH. This clinical trial confirmed that the combination treatment might be a safe and feasible choice for the treatment of early or intermediate stages of ONFH.

Purpose We investigated the effect of bilateral total hip replacement (THR) for patients with ankylosed hip joints caused by late ankylosing spondylitis (AS) and to discuss its related pre-and postoperative problems. Methods Data of 12 patients with ankylosed hip joints caused by late AS who underwent THR (24 hips) were reviewed. Each patient had both hips replaced at the same time. We assessed joint pain, range of motion (ROM) and Harris hip score (HHS) to determine postoperative results. Results Mean follow-up was 4.2 years; all hip-joint function improved, and flexion deformity was corrected. Flexion ranges were 75-105°(average 84. 4°) extension 10°~20°(average 18. 7°). HHS ranged from 15.21 points preoperation to 86.25 points postoperation. No patient experienced hip pain postoperatively, and presurgery knee and lower back pain were clearly relieved postoperatively. Conclusion Bilateral THR is an effective treatment for the ankylosed hip joint caused by late ankylosing spondylitis. When considering this procedure, attention to related preand postoperative problems must be considered.

Objective To investigate the efficacy and safety of targeted delivery of autologous bone marrow mononuclear cells (BMMCs), which are highly enriched with mesenchymal stem cells (BMMSCs), via medial circumflex femoral artery in the treatment of osteonecrosis of the femoral head (ONFH). Methods 62 patients (78 hips) with ONFH were recruited in this study. All of these patients were treated with BMMCs perfusion via medial circumflex femoral artery. The concentrated BMMCs (30–60 ml) were gained from autologous bone marrow (100–200 ml) harvested from anterior iliac crest and then were intra-arterially perfused into the femoral head. Ficat stage was used to classify the radiological stage of ONFH. Harris hip score was used to evaluate the clinical symptoms of osteonecrosis. Ficat stage and Harris hip scores were assessed at onset of treatment at 6, 12, 24, 36, 48 and 60 months after the initial treatment. Total hip arthroplasty (THA) was also assessed as an endpoint at each follow-up. Results A follow-up on the patient was done at the end of five years, and 92.31% (72 of 78) of hips achieved a satisfactory clinical result while only 6 hips (7.69%) progressed to clinical failure and required THA. Radiological progression was noted in 34 of 78 hips (43.59%); the overall rate of collapse was 38.24% (26 of 68 hips) in stage-I and stage-II hip combinations and 12.5% (2 of 16)in stage-I hips and 46.15% (24 of 52) in stage-II hips. The mean time of conversion to THA was 3 years (1 to 5 years) and the average time to collapse were 3.5 years (1–5 years). The mean Harris hip score increased from 59 points at baseline to 75 points at 12 months, 82 points at 24 months, 81 points at 36 months, 79 points at 48 months and 74 points at 60 months. Five years after the treatment, 3 of 10 hips (30%) in stage-III had deteriorated to clinical failure whereas only 3 of 68 hips (4.41%) in stage-I and II combination had progressed to clinical failure (p < 0.05). Kaplan–Meier survival analysis showed a significant difference in the time to failure between the pre-collapse hips (Ficat stage-I and II) and the post-collapse hips (Ficat stage-III) at five years follow-up (Log-rank test; p < 0.01). No complication was found in any patients. Conclusions Autologous BMMSC perfusion via the medial circumflex femoral artery can relieve symptoms, improve hip function and delay the progression of ONFH. The clinical outcome is better when it is applied prior to the collapse. This work demonstrates that autologous BMMSC perfusion via the medial circumflex femoral artery is a safe, effective and minimally invasive treatment strategy for early-stage ONFH.

In this study we investigated if Wnt/β-catenin signaling in mesenchymal progenitor cells plays a role in bone fracture repair and if DKK1-Ab promotes fracture healing through activation of β-catenin signaling. Unilateral open transverse tibial fractures were created in CD1 mice and in β-cateninPrx1ER conditional knockout (KO) and Cre-negative control mice (C57BL/6 background). Bone fracture callus tissues were collected and analyzed by radiography, micro-CT (μCT), histology, biomechanical testing and gene expression analysis. The results demonstrated that treatment with DKK1-Ab promoted bone callus formation and increased mechanical strength during the fracture healing processinCD1 mice. DKK1-Ab enhanced fracture repair by activation of endochondral ossification. The normal rate of bone repair was delayed when the β-catenin gene was conditionally deleted in mesenchymal progenitor cells during the early stages of fracture healing. DKK1-Ab appeared to act through β-catenin signaling to enhance bone repair since the beneficial effect of DKK1-Ab was abrogated in β-cateninPrx1ER conditional KO mice. Further understanding of the signaling mechanism of DKK1-Ab in bone formation and bone regeneration may facilitate the clinical translation of this anabolic agent into therapeutic intervention.

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The specific role of endogenous Bmp2 gene in chondrocytes and in osteoblasts in fracture healing was investigated by generation and analysis of chondrocyte- and osteoblast-specific Bmp2 conditional knockout (cKO) mice. The unilateral open transverse tibial fractures were created in these Bmp2 cKO mice. Bone fracture callus samples were collected and analyzed by X-ray, micro-CT, histology analyses, biomechanical testing and gene expression assays. The results demonstrated that the lack of Bmp2 expression in chondrocytes leads to a prolonged cartilage callus formation and a delayed osteogenesis initiation and progression into mineralization phase with lower biomechanical properties. In contrast, when the Bmp2 gene was deleted in osteoblasts, the mice showed no significant difference in the fracture healing process compared to control mice. These findings suggest that endogenous BMP2 expression in chondrocytes may play an essential role in cartilage callus maturation at an early stage of fracture healing. Our studies may provide important information for clinical application of BMP2.

Injectable calcium sulphate/phosphate cement (CSPC) with degradable characteristic was developed by introduction of calcium sulphate (CS) into calcium phosphate cement (CPC). The setting time, compressive strength, composition, degradation, cells and tissue responses to the CSPC were investigated. The results show that the injectable CSPC with optimum L/P ratio exhibited good injectability, and had suitable setting time and mechanical properties. Furthermore, the CSPC had good degradability and its degradation significantly faster than that of CPC in Tris-HCl solution. Cell culture results indicate that CSPC was biocompatible and could support MG63 cell attachment and proliferation. To investigate the in vivo biocompatibility and osteogenesis, the CSPC were implanted in the bone defects of rabbits. Histological evaluation shows that the introduction of CS into CPC enhanced the efficiency of new bone formation, and CSPC exhibited good biocompatibility, degradability and osteoconductivity with host bone in vivo. It can be concluded that the injectable CSPC had a significant clinical advantage over CPC, and might have potential to be applied in orthopedic, reconstructive and maxillofacial surgery, especially for minimally invasive techniques.