These data are consistent with the hypothesis that the IPFP is an osteoarthritic joint tissue capable of modulating inflammatory and destructive responses in knee-OA.

There are profound differences in secreted inflammatory factors and immune cell composition between the IFP and ScAT. These data indicate that IFP-derived soluble mediators could contribute to pathophysiological processes in the OA knee joint.

MSC chondrogenesis is inhibited by OA synovium CM through factors secreted by synovial macrophages and our findings suggest that M1 polarised subsets are potential mediators of this anti-chondrogenic effect. Modulation of macrophage phenotype may serve as a beneficial strategy to maximise the potential of MSCs for efficient cartilage repair.

Background Osteoarthritis is the most frequent chronic joint disease causing pain and disability. Besides biomechanical mechanisms, the pathogenesis of osteoarthritis may involve infl ammation, vascular alterations and dysregulation of lipid metabolism. As statins are able to modulate many of these processes, this study examines whether statin use is associated with a decreased incidence and/or progression of osteoarthritis. Methods Participants in a prospective populationbased cohort study aged 55 years and older (n=2921) were included. x-Rays of the knee/hip were obtained at baseline and after on average 6.5 years, and scored using the Kellgren and Lawrence score for osteoarthritis. Any increase in score was defi ned as overall progression (incidence and progression). Data on covariables were collected at baseline. Information on statin use during follow-up was obtained from computerised pharmacy databases. The overall progression of osteoarthritis was compared between users and non-users of statins. Using a multivariate logistic regression model with generalised estimating equation, OR and 95% CI were calculated after adjusting for confounding variables. Results Overall progression of knee and hip osteoarthritis occurred in 6.9% and 4.7% of cases, respectively. The adjusted OR for overall progression of knee osteoarthritis in statin users was 0.43 (95% CI 0.25 to 0.77, p=0.01). The use of statins was not associated with overall progression of hip osteoarthritis. Conclusions Statin use is associated with more than a 50% reduction in overall progression of osteoarthritis of the knee, but not of the hip.Osteoarthritis is the most common form of arthropathy. It affects 9.6% of men and 18% of women aged 60 years or older and is the leading cause of disability in older people. 1 2 The aetiology of osteoarthritis is not completely understood. Besides genetic variation and biomechanical mechanisms, infl ammation can lead to cartilage matrix breakdown, synovial hypertrophy, subchondral bone sclerosis and osteophyte formation. [3][4][5] The pathogenesis of osteoarthritis might also involve altered lipid metabolism and vascular pathology. [6][7][8] Current treatment of osteoarthritis consists of exercise therapy and lifestyle adjustment, with pharmacotherapeutic treatment of symptoms when needed. However, the therapeutic effi cacy of this treatment is small to moderate. 9 Until now, there is no disease-modifying compound for osteoarthritis. 5 9 In the past few decades, drug research and development has mainly focused on articular cartilage, even though the whole joint is affected in osteoarthritis and the disease process may also be infl uenced by systemic factors.In addition to lowering the circulating level of low-density lipoproteins, statins have a broad range of biological effects including anti-infl ammatory properties in different cell types. In-vitro studies revealed that statins have antioxidative effects, decrease the production of matrix metalloproteinases, interleukins and increase the production of ...

Since the first cell therapeutic study to repair articular cartilage defects in the knee in 1994, several clinical studies have been reported. An overview of the results of clinical studies did not conclusively show improvement over conventional methods, mainly because few studies reach level I of evidence for effects on middle or long term. However, these explorative trials have provided valuable information about study design, mechanisms of repair and clinical outcome and have revealed that much is still unknown and further improvements are required. Furthermore, cellular and molecular studies using new technologies such as cell tracking, gene arrays and proteomics have provided more insight in the cell biology and mechanisms of joint surface regeneration. Besides articular cartilage, cartilage of other anatomical locations as well as progenitor cells are now considered as alternative cell sources. Growth Factor research has revealed some information on optimal conditions to support cartilage repair. Thus, there is hope for improvement. In order to obtain more robust and reproducible results, more detailed information is needed on many aspects including the fate of the cells, choice of cell type and culture parameters. As for the clinical aspects, it becomes clear that careful selection of patient groups is an important input parameter that should be optimized for each application. In addition, the study outcome parameters should be improved. Although reduced pain and improved function are, from the patient's perspective, the most important outcomes, there is a need for more structure/tissue-related outcome measures. Ideally, criteria and/or markers to identify patients at risk and responders to treatment are the ultimate goal for these more sophisticated regenerative approaches in joint surface repair in particular, and regenerative medicine in general.