Increased expression of osteopontin in subchondral bone promotes bone turnover and remodeling, and accelerates the progression of OA in a mouse model.

Chuangxin Lin,Dong Guo,Shixun Li,Zhong Chen,Xinjia Wang,Yue Ding,Changchuan Li,Sipeng Lin,Laixi Zhou,Bendan Lin

doi:10.18632/aging.203707

Abstract

Osteopontin (OPN) has been proved to be closely related to the pathogenesis of osteoarthritis (OA), but the role of OPN in the pathogenesis of OA has not been fully clarified. Current studies on OPN in OA mostly focus on articular cartilage, synovial membrane and articular fluid, while ignoring its role in OA subchondral bone turnover and remodeling. In this study, we used a destabilization OA mouse model to investigate the role of OPN in OA subchondral bone changes. Our results indicate that increased expression of OPN accelerates the turnover and remodeling of OA subchondral bone, promotes the formation of h-type vessels in subchondral bone, and mediates articular cartilage degeneration induced by subchondral bone metabolism. In addition, our results confirmed that inhibition of PI3K/AKT signaling pathway inhibits OPN-mediated OA subchondral bone remodeling and cartilage degeneration. This study revealed the role and mechanism of OPN in OA subchondral bone, which is of great significance for exploring specific biological indicators for early diagnosis of OA and monitoring disease progression, as well as for developing drugs to regulate the metabolism and turnover of subchondral bone and alleviate the subchondral bone sclerosis of OA.

Highlights

Osteoarthritis (OA) is a degenerative disease caused by obesity, aging, injury, heredity and other factors, which often occurs in the elderly
We found increased expression of OPN in subchondral bone of OA patients and OA mouse models induced by ACLT+DMM
The increased expression of OPN accelerated OA subchondral bone www.aging-us.com www.aging-us.com turnover and bone remodeling, promoted the formation of h-type vessels in subchondral bone, and mediated the damage of articular cartilage caused by subchondral bone metabolism

Summary

Introduction

Osteoarthritis (OA) is a degenerative disease caused by obesity, aging, injury, heredity and other factors, which often occurs in the elderly. Long-term use of NSAIDs causes a variety of side effects affecting the gastrointestinal, renal and cardiovascular systems [4], and these treatments are limited to symptom control and www.aging-us.com remission progression, resulting in uncertain treatment outcomes in some patients with OA [5, 6]. For patients with end-stage OA and persistent severe pain, joint replacement is the only option. It would be more beneficial to focus on the early stages of OA and to prevent OA. The biggest difficulty in early diagnosis of OA is the lack of specific and sensitive biological indicators to help clinical evaluation and monitoring of disease progression, and the lack of effective early treatment drugs. Early identification and prevention of OA is the key to improve the treatment effect

Methods

Results

Conclusion