Connective tissue growth factor (CTGF/CCN2) is a member of the CCN family of matricellular proteins and also has been designated Hcs24, FISP12, IGFBP8, IGFBP-rP2, ␤IG-M2, and ecogenin. The other CCN proteins include Cyr61/CCN1, NOV/CCN3, WISP1/CCN4, WISP2/CCN5, and WISP3/CCN6 (5, 26, 38, 39) as well, and they are structurally and functionally related glycoproteins involved in cell differentiation, proliferation, adhesion, migration, and the formation of the extracellular matrix. These matricellular functions of CCNs are involved in physiological processes such as wound healing, angiogenesis, morphogenesis, and embryogenesis as well as in pathological states including fibrotic disorders, cancer, and arthritis.Earlier we showed that CCN2 promotes endochondral ossification by acting on chondrocytes, osteoblasts, and endothelial cells (35,37,46). For example, CCN2 promotes physiological chondrocytic proliferation and extracellular matrix (ECM) formation. We also reported the regeneration of defects in articular cartilage in rat knee joints following treatment with recombinant CCN2 (36). Furthermore, ctgf-null mice were dead on delivery and were characterized by defective angiogenesis, the derangement of endochondral ossification, and dysmorphisms that occurred as a result of impaired chondrocyte proliferation and an abnormal ECM composition within the hypertrophic zone (24).Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that are involved in the remodeling and turnover of the ECM in physiological processes such as angiogenesis, wound healing, embryogenesis, and morphogenesis as well as in pathological states including cancers, myocardial infarction, fibrotic disorders, rheumatism, and osteoarthritis (33, 49). Cartilage is a connective tissue that is constructed by chondrocytes embedded within an ECM predominantly composed of collagens and proteoglycans. ECM remodeling is achieved by regulating the production and degradation of specific ECM components. MMPs, which comprise a large family of enzymes with differential abilities to degrade specific ECM components, play a vital role in this process. MMPs also cleave growth factors and their binding proteins, thereby activating or inhibiting specific signaling events (15). Of note, the expression and role of MMP3 have been investigated in the pathological status of articular cartilage, such as in osteoarthritis and rheumatism (1,52).Recent study has demonstrated the existence and functions of intracellular MMPs and tissue inhibitors of metalloproteinases (TIMPs). TIMP-1 accumulates in the cellular nuclei in association with the cell cycle (54). Alternative splicing and promoter usage generate an intracellular MMP11 isoform directly translated as an active MMP (31). MMP2 is found in the nuclei of cardiac myocytes and is capable of cleaving poly-(ADP-ribose) polymerase (PARP) in vitro (28). MMP3 also is detected in the nuclei of hepatocytes and is involved in apop-* Corresponding author. Mailing address:

This study showed MMP-8 as a possible marker for progressive bone loss in peri-implantitis.

Although excessive mechanical stress is assumed to be one of the factors contributing to pathogenesis of temporomandibular joint (TMJ) osteoarthritis (OA), no pure mechanical-stress-induced OA model has been developed without surgical manipulation or puncture of the joint cavity. The purpose of this study was to establish a genuine mechanical-stress-induced OA model of the rabbit TMJ. In the experimental rabbits, repetitive, forced jaw-opening, 3 hrs/day for 5 days, was applied with the use of a general anesthesia protocol. By histological assessment of the TMJ articular tissues, partial eburnation of the articular cartilage, reactive marginal proliferation of the articular cartilage chondrocytes, and nested proliferation of chondrocytes in the subchondral bone area were observed at 7 days after the repetitive, forced-jaw-opening period. These results suggest that the repetitive, forced-jaw-opening protocol without surgical intervention can induce evident OA-like lesions in the rabbit TMJ, and this OA model may greatly contribute to the elucidation of the cartilage degradation mechanism in TMJ OA.

These findings show that CCN2/CTGF may be a suitable agent for promoting differentiation and growth of auricular chondrocytes, while preventing mineralization and apoptosis, and suggests that CCN2/CTGF may be useful for the repair or reconstruction of elastic cartilage.