miR-26a deficiency is associated with bone loss and reduced muscle strength but does not affect severity of cartilage damage in osteoarthritis

Yohei Sanada; Yasunari Ikuta; Chenyang Ding; Dilimulati Yimiti; Yoshio Kato; Tomoyuki Nakasa; Seiya Mizuno; Satoru Takahashi; Wendong Huang; Martin K Lotz; Nobuo Adachi; Shigeru Miyaki

doi:10.1016/j.mad.2023.111806

miR-26a deficiency is associated with bone loss and reduced muscle strength but does not affect severity of cartilage damage in osteoarthritis

Mech Ageing Dev. 2023 Jun:212:111806. doi: 10.1016/j.mad.2023.111806. Epub 2023 Mar 31.

Authors

Affiliations

¹ Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima 734-8552, Japan; Department of Orthopaedic Surgery, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8552, Japan.
² Department of Orthopaedic Surgery, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8552, Japan.
³ Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8566, Japan.
⁴ Laboratory Animal Resource Center in Transborder Medical Research Center, University of Tsukuba, Tsukuba 305-8575, Japan.
⁵ Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan.
⁶ Department of Diabetes Complications and Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope National Medical Center, Duarte 91010, CA, USA.
⁷ Department of Molecular Medicine, Scripps Research, La Jolla 92037, CA, USA.
⁸ Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima 734-8552, Japan; Department of Orthopaedic Surgery, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8552, Japan. Electronic address: miyaki@hiroshima-u.ac.jp.

PMID: 37003368
DOI: 10.1016/j.mad.2023.111806

Abstract

Osteoarthritis (OA) is the most common age-related joint disease. However, the role of many microRNAs (miRNA) in skeletal development and OA pathogenesis has not been sufficiently elucidated using genetically modified mice with gain- and loss-of-function models. We generated Cartilage-specific miR-26a overexpressing (Col2a1-Cre;miR-26a Tg^fl/fl: Cart-miR-26a Tg) mice and global miR-26a knockout (miR-26a KO) mice. The purpose of the present study was to determine the role of miR-26a in OA pathogenesis using aging and surgically induced models. Skeletal development of Cart-miR-26a Tg and miR-26a KO mice was grossly normal. Knee joints were evaluated by histological grading systems. In surgically-induced OA and aging models (12 and 18 months of age), Cart-miR-26a Tg mice and miR-26a KO mice exhibited OA-like changes such as proteoglycan loss and cartilage fibrillation with no significant differences in OARSI score (damage of articular cartilage) compared with control mice. However, miR-26a KO mice reduced muscle strength and bone mineral density at 12 months of age. These findings indicated that miR-26a modulates bone loss and muscle strength but has no essential role in aging-related or post-traumatic OA.

Keywords: Bone mineral density; Cartilage; Genetically modified mouse; MicroRNA; Osteoarthritis; Skeletal muscle.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cartilage, Articular*
Chondrocytes / pathology
Mice
Mice, Knockout
MicroRNAs* / genetics
Muscle Weakness
Osteoarthritis* / genetics
Osteoarthritis* / pathology

Substances

MicroRNAs

Abstract

Publication types

MeSH terms

Substances

Grants and funding