OA is one of the major complications frequently found in aged persons in advanced countries [63]. Since OA greatly affects the quality of life of these patients, exploring a novel and fundamental therapeutic strategy is earnestly desired by societies worldwide. In OA cartilage, the articular cartilage has biologically and physically disintegrated mainly due to long-term mechanical overload, buy PD0325901 in spite of the attempt of articular chondrocytes to proliferate and to produce CCN2 for repair [46]. Therefore, it would be quite reasonable to use

CCN2 as a supplement to overcome the damage to the cartilage in OA. Indeed, exogenous application of CCN2 remarkably ameliorates the OA-like changes in an experimental

rat model [12], and forced expression of CCN2 in cartilage protects the articular cartilage from OA-like damage in mice [64]. These findings indicate a solid utility of CCN2 for the treatment of OA and TMJ dysfunction (Fig. 5). The regeneration potential of CCN2 is more clearly seen from the results of experiments with another rat model. For obtaining severest damage to articular cartilage, Nishida et al. prepared rats with a full-thickness defect in their knee cartilage [12]. Exogenous application of CCN2 into the cartilage defect, in combination with gelatin hydrogel for gradual release, efficiently regenerated articular cartilage therein, without causing overgrowth. As stated in a previous section, SCH727965 CCN2 is also capable of enhancing the regeneration of auricular cartilage [32]. Indeed, the application of CCN2 onto the cultured auricular chondrocyte pellets enhances their growth in vivo as subcutaneous explants. Although no reports have

described the regeneration of damaged pinna in vivo, CCN2 may be useful in esthetic reconstruction of ears, if an appropriate drug delivery system can be established as actually done in the case of articular cartilage. In addition to the in vitro findings that CCN2 promotes the proliferation and differentiation of osteoblasts, it was also shown that CCN2 is produced at the site of regeneration after a bone fracture [3]. Since the endochondral ossification-like process recurs during the repair of a bone fracture, it may be supposed that a sustainable supply of CCN2 is made possible Nitroxoline from platelets for immediate discharge and from prehypertrophic chondrocytes for delayed production after differentiation. By mimicking this process, we are able to accelerate the regeneration of intractable bone defects. In a rat model, application of CCN2 adsorbed onto gelatin hydrogel for durable and gradual release efficiently accelerated the regeneration of intractable bone defects [13]. This is not of a great impact per se; for other factors, such as BMP-2 and FGF-2, have been indicated to be useful in promoting bone repair.