Overexpression of Pitx1 attenuates the senescence of chondrocytes from osteoarthritis degeneration cartilage:​ a self-controlled model for studying the etiology and treatment of osteoarthritis

Zhao, Xiang; Huang, Ping; Li, Gen; Feng, Yu; Zhendong, Lv; Zhou, Chun; Hu, Guangyu; Xu, Qingrong

Affiliations

¹Department of Orthopaedics, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

²Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China

³Department of Spine Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

⁴Department of Orthopaedics, Renji Hospital, School of Medicine, Shanghai JiaoTong University, 160 Pujian Road, Shanghai 200127, China

⁵Department of Orthopaedics, South Campus, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 2000, Jiangyue Road, Shanghai 201112, China

Abstract and keywords

To explore the role of low expression of Pitx1 in degenerative cartilage tissue. A cartilage injury model was established by using the cartilage scratch method. The newly generated tissue by BrdU labeled in injured cartilage region expressed SOX-9 and Col2A1 in 5-week-old rats. Compared with that, the number of BrdU-positive cells was lower in 4-month-old cartilage injury model rats. Compared with that in lateral cartilage, the expression of Pitx1 was lower in medial cartilage. Compared with chondrocytes derived from the lateral cartilage, chondrocytes derived from the medial cartilage exhibited significantly increased cell aging, as determined by SA-β-GAL staining; downregulated Pitx1 expression; reduced autophagy levels; and decreased Col2A1 expression in a chondrogenic differentiation assay. Inhibition of Pitx1 expression in chondrocytes from the lateral cartilage significantly increased the ratio of cell senescence. Overexpression of Pitx1 in chondrocytes derived from the medial cartilage decreased the cell senescence ratio. In a luciferase assay, Pitx1 was found to promote Sirt1 gene transcription. Decreased Pitx1 expression is an essential cause of cartilage degeneration in the medial tibial plateau. The described self-controlled model is an excellent way to study OA etiology and screen therapeutic drugs for OA.

Keywords: Osteoarthritis; Pitx1; Sirt1; Senescence

Links

DOI: 10.1016/j.bone.2019.115177

PubMed: 31783149

WoS: 000507697800022

History

Received: 2019-05-25

Revised: 2019-11-24

Accepted: 2019-11-25

Online: 2019-11-27

Cited Works (1)

Year	Entry
2006	Pritzker KPH, Gay S, Jimenez SA, Ostergaard K, Pelletier J-P, Revell PA, Salter D, van den Berg WB. Osteoarthritis cartilage histopathology: grading and staging. Osteoarthritis Cartilage. January 2006;14(1):13-29.