We have compared the concentrations of stromal-cell-derived factor-1 (SDF-1), matrix metalloproteinase-1 (MMP-1), MMP-9 and MMP-13 in serum before and after synovectomy or total knee replacement (TKR). We confirmed the presence of SDF-1 and its receptor CXCR4 in the synovium and articular cartilage by immunohistochemistry. We established chondrocytes by using mutant CXCR4 to block the release of MMPs.

The level of SDF-1 was decreased 5.1- and 6.7-fold in the serum of patients with OA and RA respectively, after synovectomy compared with that before surgery. MMP-9 and MMP-13 were decreased in patients with OA and RA after synovectomy. We detected SDF-1 in the synovium and the bone marrow but not in cartilage. CXCR4 was detected in articular cartilage. SDF-1 increased the release of MMP-9 and MMP-13 from chondrocytes in a dose-dependent manner. The mutant CXCR4 blocked the release of MMP-9 and MMP-13 from chondrocytes by retrovirus vector.

Synovectomy is effective in patients with OA or RA because SDF-1, which can regulate the release of MMP-9 and MMP-13 from articular chondrocytes for breakdown of cartilage, is removed by the operation.

1. Grafts of joint cartilage from immature lambs were used to repair articular cartilage defects in other lambs and in adult sheep. 2. Stability of these grafts in a functional state was found in most for periods up to fourteen months. Although a limited homograft reaction occurred this did not lead to destruction of the cartilage, even though parts of it were well vascularised. 3. The results suggest that the process of endochondral ossification is associated with the liberation of antigenic material leading to sensitisation of the host. Destruction ofthe cartilage is prevented by an inhibitory action which the matrix appears to exert on the destructive elements themselves and which is itself dependent on the vitality of the chondrocytes. 4. The avascularity of cartilage is not a sufficient explanation for its privileged position in relation to the homograft reaction

The infrequency of serious cartilage destruction in the joints of children makes it probable that the majority will recover with antibiotic and constitutional treatment alone, especially if a joint biopsy is performed. Synovectomy for children should therefore be reserved for those whose knees remain swollen and warm, even after antibiotic therapy, or whose range of movement does not show signs of returning. Exploration of such joints may show that pannus is wholly or partly covering the cartilage and that it is soft and pitted. Removal of the pannus allows better nutrition of the cartilage. The number of children who require arthrodesis in the future should be very small. Adults who respond well to antibiotic and constitutional treatment may also recover without surgery, except biopsy, but for patients with more severe disease the need for an alternative to arthrodesis exists. The choice between synovectomy–better called joint clearance –can often only be made after the joint has been opened. The choice between the two operations has always been fully discussed with the patient before the operation. The results enumerated in this paper suggest that arthrodesis may only need to be performed for patients with severe disease, often involving the bony articular surfaces, and that joints may recover function even when there has been partial destruction of cartilage

The patellofemoral joint is an important source of symptoms in osteoarthritis of the knee. We have used a newly designed surgical model of patellar strengthening to induce osteoarthritis in BALB/c mice and to establish markers by investigating the relationship between osteoarthritis and synovial levels of matrix metalloproteinases (MMPs). Osteoarthritis was induced by using this microsurgical technique under direct vision without involving the cavity of the knee. Degeneration of cartilage was assessed by the Mankin score and synovial tissue was used to determine the mRNA expression levels of MMPs. Irrigation fluid from the knee was used to measure the concentrations of MMP-3 and MMP-9. Analysis of cartilage degeneration was correlated with the levels of expression of MMP.

After operation the patellofemoral joint showed evidence of mild osteoarthritis at eight weeks and further degenerative changes by 12 weeks. The level of synovial MMP-9 mRNA correlated with the Mankin score at eight weeks, but not at 12 weeks. The levels of MMP-2, MMP-3 and MMP-14 mRNA correlated with the Mankin score at 12 weeks. An increase in MMP-3 was observed from four weeks up to 16 weeks. MMP-9 was notably increased at eight weeks, but the concentration at 16 weeks had decreased to the level observed at four weeks.

Our observations suggest that MMP-2, MMP-3 and MMP-14 could be used as markers of the progression of osteoarthritic change.

Ketamine has been used in combination with a variety of other agents for intra-articular analgesia, with promising results. However, although it has been shown to be toxic to various types of cell, there is no available information on the effects of ketamine on chondrocytes.

We conducted a prospective randomised controlled study to evaluate the effects of ketamine on cultured chondrocytes isolated from rat articular cartilage. The cultured cells were treated with 0.125 mM, 0.250 mM, 0.5 mM, 1 mM and 2 mM of ketamine respectively for 6 h, 24 hours and 48 hours, and compared with controls. Changes of apoptosis were evaluated using fluorescence microscopy with a 490 nm excitation wavelength. Apoptosis and eventual necrosis were seen at each concentration. The percentage viability of the cells was inversely proportional to both the duration and dose of treatment (p = 0.002 and p = 0.009). Doses of 0.5 mM, 1 mM and 2mM were absolutely toxic.

We concluded that in the absence of solid data to support the efficacy of intra-articular ketamine for the control of pain, and the toxic effects of ketamine on cultured chondrocytes shown by this study, intra-articular ketamine, either alone or in combination with other agents, should not be used to control pain.

Cite this article: Bone Joint J 2014; 96-B:989–94.

Previous studies support the important role of vascular endothelial growth factor (VEGF) and syndecan-4 in the pathogenesis of osteoarthritis (OA). Both VEGF and syndecan-4 are expressed by chondrocytes and both are involved in the regulation of matrix metalloproteinase-3, resulting in the activation of aggrecanase II (ADAMTS-5), which is essential in the pathogenesis of OA. However, the relationship between VEGF and syndecan-4 has not been established. As a pilot study, we assayed the expression of VEGF and syndecan-4 in cartilage samples and cultured chondrocytes from osteoarthritic knee joints and analysed the relationship between these two factors.

Specimens were collected from 21 female patients (29 knees) who underwent total knee replacement due to severe medial OA of the knee (Kellgren–Lawrence grade 4). Articular cartilage samples, obtained from bone and cartilage excised during surgery, were analysed and used for chondrocyte culture. We found that the levels of expression of VEGF and syndecan-4 mRNA did not differ significantly between medial femoral cartilage with severe degenerative changes and lateral femoral cartilage that appeared grossly normal (p = 0.443 and 0.622, respectively). Likewise, the levels of expression of VEGF and syndecan-4 mRNA were similar in cultured chondrocytes from medial and lateral femoral cartilage. The levels of expression of VEGF and syndecan-4 mRNAs were significantly and positively correlated in cartilage explant (r = 0.601, p = 0.003) but not in cultured chondrocytes. These results suggest that there is a close relationship between VEGF and syndecan-4 in the cartilage of patients with OA. Further studies are needed to determine the exact pathway by which these two factors interact in the pathogenesis of OA.

Cite this article: Bone Joint J 2014;96-B:1319–24.

The pathophysiology of intervertebral disc degeneration has been extensively studied. Various factors have been suggested as influencing its aetiology, including mechanical factors, such as compressive loading, shear stress and vibration, as well as ageing, genetic, systemic and toxic factors, which can lead to degeneration of the disc through biochemical reactions. How are these factors linked? What is their individual importance? There is no clear evidence indicating whether ageing in the presence of repetitive injury or repetitive injury in the absence of ageing plays a greater role in the degenerative process. Mechanical factors can trigger biochemical reactions which, in turn, may promote the normal biological changes of ageing, which can also be accelerated by genetic factors. Degradation of the molecular structure of the disc during ageing renders it more susceptible to superimposed mechanical injuries.

This review supports the theory that degeneration of the disc has a complex multifactorial aetiology. Which factors initiate the events in the degenerative cascade is a question that remains unanswered, but most evidence points to an age-related process influenced primarily by mechanical and genetic factors.

The use of joint-preserving surgery of the hip has been largely abandoned since the introduction of total hip replacement. However, with the modification of such techniques as pelvic osteotomy, and the introduction of intracapsular procedures such as surgical hip dislocation and arthroscopy, previously unexpected options for the surgical treatment of sequelae of childhood conditions, including developmental dysplasia of the hip, slipped upper femoral epiphysis and Perthes’ disease, have become available. Moreover, femoroacetabular impingement has been identified as a significant aetiological factor in the development of osteoarthritis in many hips previously considered to suffer from primary osteoarthritis.

As mechanical causes of degenerative joint disease are now recognised earlier in the disease process, these techniques may be used to decelerate or even prevent progression to osteoarthritis. We review the recent development of these concepts and the associated surgical techniques.

Cite this article: Bone Joint J 2014;96-B:5–18.

We reviewed three infants with destructive osteomyelitis involving the proximal tibial epiphysis at a follow-up of eight to 22 years. All cases showed early radiographic destructive changes in the medial or lateral aspects of the epiphysis and metaphysis. Despite the ominous early appearance of the epiphysis, all cases showed spontaneous re-ossification of the epiphysis with restoration of the tibial condyle and preservation of joint congruity. The patients, however, developed a valgus or varus deformity which was treated satisfactorily with one to three proximal tibial osteotomies. The potential for regeneration of the epiphysis following infantile osteomyelitis of the proximal tibia suggests these cases should be treated expectantly with regard to joint congruity.