The Interaction between Joint Inflammation and Cartilage Repair

BACKGROUND: Articular cartilage lesions occur frequently but unfortunately damaged cartilage has a very limited intrinsic repair capacity. Therefore, there is a high need to develop technology that makes cartilage repair possible. Since joint damage will lead to (sterile) inflammation, development of this technology has to take into account the effects of inflammation on cartilage repair. METHODS: A literature search has been performed including combinations of the following keywords; cartilage repair, fracture repair, chondrogenesis, (sterile) inflammation, inflammatory factors, macrophage, innate immunity, and a number of individual cytokines. Papers were selected that described how inflammation or inflammatory factors affect chondrogenesis and tissue repair. A narrative review is written based on these papers focusing on the role of inflammation in cartilage repair and what we can learn from findings in other organs, especially fracture repair. RESULTS: The relationship between inflammation and tissue repair is not straightforward. Acute, local inflammation stimulates fracture repair but appears to be deleterious for chondrogenesis and cartilage repair. Systemic inflammation has a negative effect on all sorts of tissue repair. CONCLUSION: Findings on the role of inflammation in fracture repair and cartilage repair are not in line. The currently widely used models of chondrogenesis, using high differentiation factor concentrations and corticosteroid levels, are not optimal. To make it possible to draw more valid conclusions about the role of inflammation and inflammatory factors on cartilage repair, model systems must be developed that better mimic the real conditions in a joint with damaged cartilage.

Differential Role of Transforming Growth Factor-beta in an Osteoarthritic or a Healthy Joint

Transforming growth factor-β (TGF-β) is a cytokine that plays an important role in both normal joints and joints affected by osteoarthritis (OA), the most common joint disease. However, the role of this pleiotropic cytokine in a normal healthy joint is very different from its role in an OA joint. In a normal synovial joint, active TGF-β is only present after joint loading and only for a short period. In contrast, permanent and high levels of active TGF-β are detected in OA joints. Due to this difference in levels and exposure period of joint cells to active TGF-β, the function of TGF-β is strikingly different in normal and OA joints. The consequences of this difference in TGF-β levels on joint homeostasis and pathological changes in OA joints are discussed in this review.