XMU-MP-1 attenuates osteoarthritis via inhibiting cartilage degradation and chondrocyte apoptosis

Xue Hao; Jing Zhao; Liyuan Jia; Ting He; Huanbo Wang; Jing Fan; Yating Yang; Fei Su; Qingda Lu; Chao Zheng; Liu Yang; Qiang Jie

doi:10.3389/fbioe.2022.998077

XMU-MP-1 attenuates osteoarthritis via inhibiting cartilage degradation and chondrocyte apoptosis

Front Bioeng Biotechnol. 2022 Sep 19:10:998077. doi: 10.3389/fbioe.2022.998077. eCollection 2022.

Authors

Xue Hao^{1

2

3}, Jing Zhao⁴, Liyuan Jia⁴, Ting He⁵, Huanbo Wang⁶, Jing Fan⁶, Yating Yang^{1

2

3}, Fei Su^{1

2

3}, Qingda Lu^{1

2

3}, Chao Zheng⁶, Liu Yang⁶, Qiang Jie^{1

2

3}

Affiliations

¹ Pediatric Orthopaedic Hospital, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China.
² Research Center for Skeletal Developmental Deformity and Injury Repair, School of Life Science and Medicine, Northwest University, Xi'an, China.
³ Clinincal Research Center for Pediatric Skeletal Deformity and Injury of Shaanxi Province, Xi'an, China.
⁴ College of Life Sciences, Northwest University, Xi'an, China.
⁵ Medical Research Institute, Northwestern Polytechnical University, Xi'an, China.
⁶ Institute of Orthopedic Surgery, Xijing Hospital, Air Force Medical University, Xi'an, China.

Abstract

Osteoarthritis (OA) is the most prevalent type of degenerative joint disease; it is reported to be associated with inflammatory responses, chondrocyte apoptosis, and cartilage degeneration. XMU-MP-1 is a selective MST1/2 inhibitor which activates the downstream effector YAP and promotes cell growth. It has displayed excellent benefits in mouse intestinal repair, as well as liver repair and regeneration. However, the effects of XMU-MP-1 on OA remain unclear. In this study, we investigated the therapeutic role of XMU-MP-1 on interleukin-1β (IL-1β)-induced inflammation in mice chondrocytes and the destabilization of the medial meniscus surgery (DMM)-induced OA model. In chondrocytes, treatment with XMU-MP-1 elevated the matrix metalloproteinases (Mmp3, Mmp13) and decreased the extracellular matrix (Col2, Acan) induced by IL-1β. Moreover, XMU-MP-1 strongly inhibited IL-1β-induced chondrocyte apoptosis and significantly promoted chondrocyte proliferation. Furthermore, XMU-MP-1 demonstrated a protective and therapeutic influence on the mouse OA model. These findings indicate that XMU-MP-1 may have a protective effect on cartilage degradation and may be a new potential therapeutic option for OA.

Keywords: Hippo signaling; XMU-MP-1; cartilage; chondrocyte; osteoarthritis.