Back to Search Start Over

Malat1 attenuated the rescuing effects of docosahexaenoic acid on osteoarthritis treatment via repressing its chondroprotective and chondrogenesis activities

Authors :
Lu Feng
Zhengmeng Yang
Yucong Li
Nan Hou
Boguang Yang
Xuan Lu
Shanshan Bai
Ming Wang
Xiaoting Zhang
Haixing Wang
Yaofeng Wang
Micky D. Tortorella
Gang Li
Source :
Biomedicine & Pharmacotherapy, Vol 154, Iss , Pp 113608- (2022)
Publication Year :
2022
Publisher :
Elsevier, 2022.

Abstract

Osteoarthritis (OA) is a degenerative disease associated with joint inflammation, articular cartilage degeneration and subchondral hypertrophy. Small molecules which both ameliorate chondrocyte OA phenotype and activate bone marrow-derived mesenchymal stem cells (BMSCs) chondrogenesis under inflammatory conditions have the therapeutical potential for OA treatment. In this study, we characterized a novel small molecule which could ameliorate OA progression via novel regulating mechanisms. Docosahexaenoic acid (DHA), a bioactive molecule, was screened from a small molecule library and showed anti-inflammatory and chondroprotective effects in OA chondrocytes, as well as ameliorated IL-1β impaired BMSCs chondrogenesis in Wnt/β-catenin and NF-κB signaling dependent manners. Furthermore, Malat1 was found to be the key mediator of DHA-mediating anti-inflammation chondroprotection and chondrogenesis. DHA also rescued cartilage loss and damage in a surgery-induced OA mice model. The elevation of serum Malat1 levels caused by OA was also downregulated by DHA treatment. Taken together, our findings demonstrated that DHA, with a dual-signaling repression property, exerted its anti-inflammation, chondroprotection and chondrogenesis function possibly via regulating Malat1 level, suggesting that it may be a possible drug candidate for OA patients with elevated MALAT1 expression levels.

Details

Language :
English
ISSN :
07533322
Volume :
154
Issue :
113608-
Database :
Directory of Open Access Journals
Journal :
Biomedicine & Pharmacotherapy
Publication Type :
Academic Journal
Accession number :
edsdoj.907b07e74173410cb7f174e38deee3fc
Document Type :
article
Full Text :
https://doi.org/10.1016/j.biopha.2022.113608