Considering the role of osteocytes in maintaining the bone matrix network and in that regulating bone metabolism for correct bone homeostasis, the effect of aminobisphosphonates on these cells is very interesting. However, further studies are needed to elucidate the effective action of drugs on these cells. Moreover, COX 2 expression is significantly increased in osteocytes and in bone marrow Inhibitors,Modulators,Libraries cells after Ris treat ment. These results suggest COX 2 as an important tar get of Ris and support the hypothesis that aminobisphosphonates may have an anabolic effect on bone by increasing both the lifespan and the number of active osteogenic cells. Osteoarthritis is a degenerative joint disease and is a major cause of disability. Currently, there Inhibitors,Modulators,Libraries is no treatment capable of altering its progression.

The major pathological characteristics Inhibitors,Modulators,Libraries of OA include progressive loss of articular cartilage, osteophyte formation, and changes in peri articular and subchondral bone. The articular cartilage receives most of the attention in OA studies because Inhibitors,Modulators,Libraries the primary pathologic feature seen in OA is gross articular cartilage damage. Matrix metalloproteinase 13 is a major enzyme that targets cartilage for degradation. Compared to other MMPs, the expression of MMP13 is more restricted to connective tissue. It not only targets type II collagen in cartilage for degradation, but also degrades proteoglycan, types IV and type IX collagen, osteonectin and perlecan in cartilage. Clinical investigation revealed that patients with articular cartilage destruction have high MMP13 expression, suggesting that increased MMP13 may be associated with cartilage degradation.

Studies have also shown that Mmp13 overexpressing transgenic mice develop a spontaneous OA like articular cartilage destruc tion phenotype. The ADAMTS family of aggrecanases Inhibitors,Modulators,Libraries also contributes to proteoglycan aggrecan depletion and are associated with cartilage degradation during OA. ADAMTS4 and 5 were identified as the major aggrecanases during OA development. Deletion of the Adamts5 gene or double knockout of Adamts4 and Adamts5 prevented cartilage degradation in a surgically induced murine knee OA model. These findings indi cate that catabolic enzymes play a significant role in OA progression and support the development of therapies tar geting these enzymes as a strategy to decelerate articular cartilage degradation.

Meniscal injuries are among the most common causes of post traumatic OA in humans. The meniscus is a C shaped cartilage that functions as a shock inhibitor Sunitinib absorbing, load bearing, stability enhancing, and lubricating cush ion in the knee joint. Studies show that loss of meniscus integrity and function leads to OA in humans. The meniscal ligamentous injury induced murine OA model was initially developed by Clements et al. and this injury model has been further modified and developed in recent studies.