β-Ecdysone attenuates cartilage damage in a
mouse model of collagenase-induced osteoarthritis via mediating FOXO1/ADAMTS-4/5 signaling axis
Junzhu Han1,2, Jianzhong Guan1,3 and Xunbing Zhu2,4
1Department of Orthopedics, Jinan University, Guangzhou, Guangdong Province, 2Department of Orthopedics, the Second Affiliated Hospital of Bengbu Medical College, 3Department of Orthopedics, the First Affiliated Hospital of Bengbu Medical College and 4Anhui Key Laboratory of Tissue Transplantation, Bengbu, Anhui Province, China
Corresponding Author: Dr. Jianzhong Guan, Department of Orthopedics, the First Affiliated Hospital of Bengbu Medical College, No. 287 Changhuai Road, Bengbu 233000, Anhui Province, China. e-mail: jzguan2002@163.com
Summary. Background. β-Ecdysone has been reported to perform a protective effect to prevent interleukin 1β (IL-1β)-induced apoptosis and inflammatory response in chondrocytes. In our study, the chondroprotective effects of β-Ecdysone were explored in a mouse model of collagenase-induced osteoarthritis (OA).
Methods. Injection of collagenase in the left knee was implemented to establish a mouse model of OA. The histomorphological analysis was detected using safranine O staining. Serum pro-inflammatory cytokines were measured by ELISA assays. Protein expression in the femur and chondrocytes was analyzed using western blot. Chondrocyte apoptosis was evaluated by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) staining.
Results. Treatment of OA mice with β-Ecdysone supplementation significantly inhibited the production of pro-inflammatory cytokines. Histologic examination exhibited that the degradation of proteoglycans and the loss of trabecular bone were observed in collagenase-injected mice. However, OA-like changes were attenuated by β-Ecdysone administration in collagenase-injected mice. Both in vivo and in vitro models, nuclear forkhead box O1 (FOXO1) protein expression was significantly reduced in the femur of collagenase-treated mice and IL-1β-stimulated chondrocytes. However, β-Ecdysone treatment was able to rescue FOXO1 protein expression in the nucleus to inhibit the transcription and translation of a disintegrin-like and metallopeptidase (reprolysin type) with thrombospondin type 1 motif, 4 (ADAMTS-4) and ADAMTS-5.
Conclusion. The findings suggested that β-Ecdysone functioned as a FOXO1 activator to protect collagenase-induced cartilage damage. FOXO1 might be a potential molecular target of β-Ecdysone for the effective prevention and treatment of OA. Histol Histopathol 36, 785-794 (2021)
Key words: β-Ecdysone, Osteoarthritis, FOXO1, Chondrocyte
DOI: 10.14670/HH-18-341
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©The Author(s) 2021. Open Access. This article is licensed under a Creative Commons CC-BY International License. |
