WITHDRAWN: Aging upregulates CCN-1 expression leading to cell senescence and tissue degenerative changes in tendons

Abstract

// Qibin Song 1 , Zhe Wang 2 , Yuling Wang 1 and Abdul Razaq 3 1 Department of Plastic Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, P.R. China 2 Department of Pathology, Shengjing Hospital of China Medical University, Shenyang 110004, P.R. China 3 Department of Dermatology, Shengjing Hospital of China Medical University, Shenyang 110004, P.R. China Correspondence to: Qibin Song, email: sqb_cmu1@163.com Keywords: CCN-1; aging; tendon stem cell; senescence; differentiation Received: September 06, 2017 Accepted: December 22, 2017 Published: January 02, 2018 ABSTRACT Aging leads to degenerative changes in tissues and organs. Tendinopathy is a kind of tendon degenerative diseases found commonly in aging populations. A matricellular protein, CCN family member-1 (CCN-1) plays an important role in cell proliferation and differentiation. However, the precise cellular mechanisms responsible for the effects of CCN-1 on tendons, especially aging tendons are largely unknown. In this study we investigated the effects of aging and CCN-1 on tendon stem/progenitor cells (TSCs) of young (3 and 6 months old) and aging (12 and 18 months old) rats. We found CCN-1 expression markedly enhanced in rat tendons in an age-dependent manner. The CCN-1 mRNA was 5 times higher in 18 months old tendons than that of 3 months old tendons. Aging also increased cell senescence, decreased proliferation and “stemness” of the TSCs. Furthermore, CCN-1 treatment of young TSCs exhibited similar results found in aging TSCs. The expression of SA-β-Gal on young TSCs treated with CCN-1 significantly increased in a CCN-1 concentration-dependent manner. Moreover, some senescence-related genes, such as IL-1α, IL-1β, IL-6, TNF-α, IP-10, MMP-13, and GRO-1, were also increased in CCN-1 treated young TSCs in a CCN-1 concentration-dependent manner. These results were further verified with western blot. On the other hand, tenocyte-related genes including collagen type I and tenomodulin were decreased in young TSCs treated with CCN-1. Our findings indicate that CCN-1 plays an important role in degenerative tendon diseases. The inhibition of CCN-1 may slow down aging tendon degenerations and provide a new approach for treatment of tendon diseases.