Mir-381-3p aggravates ovariectomy-induced osteoporosis by inhibiting osteogenic differentiation through targeting KLF5/Wnt/β-catenin signaling pathway.

Autor: Zhao Y; Department of Orthopedic surgery, The First Affiliated Hospital of Harbin Medical University, No.23, Youzheng Street, Nangang District, Harbin, Heilongjiang, 150001, China.; Department of Orthopedic surgery, The Fifth Hospital of Harbin, Harbin, Heilongjiang, 150036, China., Liu J; Department of Orthopedic surgery, The First Affiliated Hospital of Harbin Medical University, No.23, Youzheng Street, Nangang District, Harbin, Heilongjiang, 150001, China., Zhang Y; Department of Orthopedic surgery, The First Affiliated Hospital of Harbin Medical University, No.23, Youzheng Street, Nangang District, Harbin, Heilongjiang, 150001, China., Liang M; Department of Orthopedic surgery, The First Affiliated Hospital of Harbin Medical University, No.23, Youzheng Street, Nangang District, Harbin, Heilongjiang, 150001, China., Li R; Department of Orthopedic surgery, The First Affiliated Hospital of Harbin Medical University, No.23, Youzheng Street, Nangang District, Harbin, Heilongjiang, 150001, China.; Spinal Surgery Department, BinZhou Medical University Hospital, Binzhou, Shandong, 256603, China., Song Y; Department of Orthopedic surgery, The First Affiliated Hospital of Harbin Medical University, No.23, Youzheng Street, Nangang District, Harbin, Heilongjiang, 150001, China.; The LiWan Central Hospital of Guang Zhou, Guangzhou, Guangdong, 510000, China., Wang Y; Department of Orthopedic surgery, The First Affiliated Hospital of Harbin Medical University, No.23, Youzheng Street, Nangang District, Harbin, Heilongjiang, 150001, China. wangyansong_w@126.com.
Jazyk: angličtina
Zdroj: Journal of orthopaedic surgery and research [J Orthop Surg Res] 2024 Aug 17; Vol. 19 (1), pp. 480. Date of Electronic Publication: 2024 Aug 17.
DOI: 10.1186/s13018-024-04992-6
Abstrakt: Background: Increasing evidence shows the pivotal significance of miRNAs in the pathogenesis of osteoporosis. miR-381-3p has been identified as an inhibitor of osteogenesis. This study explored the role and mechanism of miR-381-3p in postmenopausal osteoporosis (PMOP), the most common type of osteoporosis.
Methods: Bilateral ovariectomy (OVX) rat model was established and miR-381-3p antagomir was administrated through the tail vein in vivo. The pathological changes in rats were assessed through the evaluation of serum bone turnover markers (BALP, PINP, and CTX-1), hematoxylin and eosin (H&E) staining, as well as the expression of osteoblast differentiation biomarkers. Moreover, isolated bone marrow mesenchymal stem cells from OVX-induced rats (OVX-BMMSCs) were utilized to explore the impact of miR-381-3p on osteoblast differentiation. In addition, the target gene and downstream pathway of miR-381-3p were further investigated both in vivo and in vitro.
Results: miR-381-3p expression was elevated, whereas KLF5 was suppressed in OVX rats. miR-381-3p antagomir decreased serum levels of bone turnover markers, improved trabecular separation, promoted osteoblast differentiation biomarker expression in OVX rats. ALP activity and mineralization were suppressed, and levels of osteoblast differentiation biomarkers were impeded after miR-381-3p overexpression during osteoblast differentiation of OVX-BMMSCs. While contrasting results were found after inhibition of miR-381-3p. miR-381-3p targets KLF5, negatively affecting its expression as well as its downstream Wnt/β-catenin pathway, both in vivo and in vitro. Silencing of KLF5 restored Wnt/β-catenin activation induced by miR-381-3p antagomir.
Conclusion: miR-381-3p aggravates PMOP by inhibiting osteogenic differentiation through targeting KLF5/Wnt/β-catenin pathway. miR-381-3p appears to be a promising candidate for therapeutic intervention in PMOP.
(© 2024. The Author(s).)
Databáze: MEDLINE
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