Abstract
Osteoarthritis, also known as degenerative arthritis or degenerative joint disease, causes pain and disability worldwide. Cartilage regeneration is key to finding a cure for this disease. Adipose-derived stem cells (ASCs) are capable of differentiating into cartilage lineages in vitro and they have shown promise in the field of regenerative medicine. However, the underlying mechanisms remain unclear. In this study, we demonstrated that miR-194 levels gradually decreased during the chondrogenic differentiation of human ASCs (hASCs). After predicting the target of miR-194 using Pictar and Targetscan, we hypothesized that Sox5 is potentially the key link between miR-194 and the chondrogenesis of ASCs. Initially, we demonstrated that Sox5 is a target of miR194 according to luciferase assay analysis. We further demonstrated that the differentiation of ASCs can be controlled by miR-194 through gain or loss of function experiments, and we observed that the down-regulation of miR-194 increases its direct target gene, Sox5, and results in enhanced chondrogenic differentiation of hASCs, whereas up-regulation decreases Sox5 and inhibits chondrogenesis. We also found that miR-194 correlates with Sox5 in osteoarthritis. These findings, taken together, are the first to illustrate the critical role of miR-194 in hASC chondrogenesis, and may provide novel insight beneficial to cell manipulation methods during cartilage regeneration.
Highlights
Age-related osteoarthritis (OA) is widely recognized as the most common form of arthritis and one of the leading causes of pain and disability worldwide
Using miR microarray analysis, we demonstrated that miR-194 gradually decreased during chondrogenesis of Adipose-derived stem cells (ASCs), the differential expression pattern was confirmed by qRT-PCR assay
Because SRY-related high mobility group-Box gene 5 (Sox5) plays an essential role in chondrogenesis, we focused on the relationships among miR-194, Sox5, and chondrogenesis
Summary
Age-related osteoarthritis (OA) is widely recognized as the most common form of arthritis and one of the leading causes of pain and disability worldwide. Adipose-derived stem cells (ASCs) have shown promise in the field of regenerative medicine and are reported to exhibit stable proliferation kinetics and to exhibit the capacity to differentiate into various lineages in vitro [2]. Compared to bone marrow, which is widely used to isolate bone marrowderived stem cells (MDSCs), adipose tissue holds the advantage of being obtained and being conducive for the separation of stem cells from the harvested tissue [3]. The ability to successfully direct ASCs toward cartilage lineage differentiation provides considerable progress toward the regeneration of articular cartilage [4]. Elucidation of the mechanisms underlying cartilage differentiation from adult stem cells may potentially prevent further cartilage destruction and activate the repair of cartilage lesions
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