CCN3 (NOV) Drives Degradative Changes in Aging Articular Cartilage.

Research paper by Miho M Kuwahara, Koichi K Kadoya, Sei S Kondo, Shanqi S Fu, Yoshiko Y Miyake, Ayako A Ogo, Mitsuaki M Ono, Takayuki T Furumatsu, Eiji E Nakata, Takako T Sasaki, Shogo S Minagi, Masaharu M Takigawa, Satoshi S Kubota, Takako T Hattori

Indexed on: 22 Oct '20Published on: 18 Oct '20Published in: International journal of molecular sciences


Aging is a major risk factor of osteoarthritis, which is characterized by the degeneration of articular cartilage. CCN3, a member of the CCN family, is expressed in cartilage and has various physiological functions during chondrocyte development, differentiation, and regeneration. Here, we examine the role of CCN3 in cartilage maintenance. During aging, the expression of mRNA in mouse primary chondrocytes from knee cartilage increased and showed a positive correlation with and mRNA. Increased accumulation of CCN3 protein was confirmed. To analyze the effects of CCN3 , either primary cultured human articular chondrocytes or rat chondrosarcoma cell line (RCS) were used. Artificial senescence induced by HO caused a dose-dependent increase in gene and CCN3 protein expression, along with enhanced expression of and mRNA and proteins, as well as SA-β gal activity. Overexpression of CCN3 also enhanced promoter activity via . Accordingly, the addition of recombinant CCN3 protein to the culture increased the expression of and mRNAs. We have produced cartilage-specific CCN3-overexpressing transgenic mice, and found degradative changes in knee joints within two months. Inflammatory gene expression was found even in the rib chondrocytes of three-month-old transgenic mice. Similar results were observed in human knee articular chondrocytes from patients at both mRNA and protein levels. These results indicate that CCN3 is a new senescence marker of chondrocytes, and the overexpression of CCN3 in cartilage may in part promote chondrocyte senescence, leading to the degeneration of articular cartilage through the induction of p53 and p21.