This CCN2 induction seems to be mediated in part by macrophage-colony stimulating factor (M-CSF), also suggesting an unexpected anabolic functional aspect of this molecule in cartilage [47]. According to the fact that

CCN2 promotes the proliferation and ECM-molecule production of articular chondrocytes in vitro, it is reasonable to consider that CCN2 is induced to reconstruct the damaged articular cartilage. Conversely, cartilaginous ECM degradation is directly carried out by proteases, such as MMPs and ADAM-TS5. It is known that mechanical injury buy A-1210477 induces the production of FGF-2 in articular cartilage, which subsequently provokes the production of a number of MMPs including MMP-13. It is important to note that a recent

study revealed the molecular interplay between CCN2 and FGF-2 in cartilage [48]. Thus, CCN2 is believed to reorganize the articular cartilage architecture against external stress to maintain its integrity under collaboration with other signaling molecules such as FGF-2. Upon oral tissue injury, the Idelalisib wounded areas are primarily filled with blood clot with polymerized fibrin molecules formed through the activation of platelets and the coagulation cascade. Subsequently, fibroblasts migrate therein and occasionally differentiate into myofibroblasts to produce fibrotic ECM molecules such as type I collagen. This process may be followed by the contraction of the wounded area by α-smooth muscle actin-positive myofibroblasts. During this tissue regeneration process, CCN2 is supplied by multiple sources and plays central roles in the regeneration. Although CCN2 is abundantly encapsulated in platelets and released upon activation of them [25], it is also endogenously

produced by the cells around the injured area. In fact, strong expression of the CCN2 gene is observed in the tooth extraction sockets [49], as well as in the wounded dermal tissue [50]. Data obtained in vitro showed that CCN2 enhances the synthesis of type I collagen in fibroblasts and periodontal ligament cells [51] and [52], further supporting Protirelin this notion. Tissue fibrosis, which is characterized by the abnormal accumulation of a vast amount of fibrous ECM and functional deficiency, can be regarded as an unsuccessful outcome of continuous tissue remodeling toward reconstruction. Consistently, CCN2 is known to be a key molecule that develops fibrotic disorders in a variety of organs. The target organs in humans include most tissues and organs including liver, kidney, lungs, pancreas, and heart as well as orofacial tissues, save for neuronal and genital ones [1], [4] and [7]. Over the past 10 years, CCN2 has been attracting the interest of dermatologists, since it mediates the pathological changes observed in progressive systemic sclerosis or scleroderma [4], [53] and [54].