Dual functions of microRNA-17 in maintaining cartilage homeostasis and protection against osteoarthritis

Yun Zhang, Shuaijun Li, Peisheng Jin, Ting Shang, Ruizhu Sun, Laiya Lu, Kaijin Guo, Jiping Liu, Yongjuan Tong, Junbang Wang, Sanhong Liu, Chen Wang, Yubin Kang, Wenmin Zhu, Qian Wang, Xiaoren Zhang, Feng Yin, Yi Eve Sun () and Lei Cui ()
Additional contact information
Yun Zhang: Tongji University School of Medicine
Shuaijun Li: Tongji University School of Medicine
Peisheng Jin: Affiliated Hospital of Xuzhou Medical University
Ting Shang: Capital Medical University
Ruizhu Sun: Tongji University School of Medicine
Laiya Lu: Tongji University School of Medicine
Kaijin Guo: Affiliated Hospital of Xuzhou Medical University
Jiping Liu: Tongji University School of Medicine
Yongjuan Tong: Capital Medical University
Junbang Wang: Tongji University School of Medicine
Sanhong Liu: ShanghaiTech University
Chen Wang: ShanghaiTech University
Yubin Kang: Capital Medical University
Wenmin Zhu: Tongji University School of Medicine
Qian Wang: Tongji University School of Medicine
Xiaoren Zhang: Affiliated Cancer Hospital & Institute of Guangzhou Medical University
Feng Yin: Tongji University School of Medicine
Yi Eve Sun: Tongji University School of Medicine
Lei Cui: Tongji University School of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: Abstract Damaged hyaline cartilage has no capacity for self-healing, making osteoarthritis (OA) “difficult-to-treat”. Cartilage destruction is central to OA patho-etiology and is mediated by matrix degrading enzymes. Here we report decreased expression of miR-17 in osteoarthritic chondrocytes and its deficiency contributes to OA progression. Supplementation of exogenous miR-17 or its endogenous induction by growth differentiation factor 5, effectively prevented OA by simultaneously targeting pathological catabolic factors including matrix metallopeptidase-3/13 (MMP3/13), aggrecanase-2 (ADAMTS5), and nitric oxide synthase-2 (NOS2). Single-cell RNA sequencing of hyaline cartilage revealed two distinct superficial chondrocyte populations (C1/C2). C1 expressed physiological catabolic factors including MMP2, and C2 carries synovial features, together with C3 in the middle zone. MiR-17 is highly expressed in both superficial and middle chondrocytes under physiological conditions, and maintains the physiological catabolic and anabolic balance potentially by restricting HIF-1α signaling. Together, this study identified dual functions of miR-17 in maintaining cartilage homeostasis and prevention of OA.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-30119-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30119-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-30119-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().