MiR-30b-5p Influences Chronic Exercise Arthritic Injury by Targeting Hoxa1

Abstract

We identified the role of miR-30b-5p in chronic exercise arthritic injury. Rats with chronic exercise arthritic injury received treatment with miR-30b-5p antagomiR. H&E and Safranin O-fast green staining were performed. The levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were detected. The binding relationship between homeobox A1 (Hoxa1) and miR-30b-5p was revealed. After manipulating the expressions of miR-30b-5p and/or Hoxa1 in chondrocytes, the viability, apoptosis and migration of chondrocytes were assessed. The levels of molecules were determined by qRT-PCR or Western blot. MiR-30b-5p antagomiR ameliorated articular cartilage lesion and destruction, reduced Mankin’s score and the levels of TNF-α, IL-1β, miR-30b-5p, matrix metallopeptidase 13 (MMP-13), and cleaved caspase-3, and increased relative thickness and the levels of Hoxa1, Aggrecan and type II collagen (COLII) in model rats. MiR-30b-5p up-regulation decreased Hoxa1 level, viability, migration and induced apoptosis, whereas miR-30b-5p down-regulation produced the opposite effects. MiR-30b-5p up-regulation increased the levels of MMP-13 and cleaved caspase-3, but decreased those of Aggrecan and COLII in chondrocytes. However, the action of miR-30b-5p up-regulation on chondrocytes was reversed by Hoxa1 overexpression. In conclusion, miR-30b-5p is involved in cartilage degradation in rats with chronic exercise arthritic injury and regulates chondrocyte apoptosis and migration by targeting Hoxa1.

MiR-30 Family: A Novel Avenue for Treating Bone and Joint Diseases?

“…Second, miR-30a/b promoted the inflammatory response and ECM degradation by enhancing the expression of IL-1β during chondrogenic differentiation 41 , 26 . Other evidence showed that miR-30b-5p increased the protein levels of MMP-13, cleaved caspase-3 and TNF-α in chondrocytes 37 . All these factors could strongly promote ECM degradation.…”

“…Recently, studies confirmed that miR-30a/b was upregulated in OA cartilage samples, which promoted OA progression by inhibiting chondrocyte proliferation and differentiation, and promoting inflammation and extracellular matrix (ECM) degradation. First, miR-30b could downregulate the mRNA expression of collagen alpha-1(II) chain and aggrecan, which are key factors for cartilage proliferation and differentiation 37 . This effect was accomplished by targeting SOX9 38 , 39 and ERG (ETS-related gene) mRNA 40 .…”

“…All these factors could strongly promote ECM degradation. In a rat model of chronic exercise arthritic injury, Li et al found that miR-30b-5p could regulate the inflammation, apoptosis and migration of chondrocytes by targeting Hoxa1 mRNA 37 . In addition, among the upstream genes of the miR-30 family, LncRNA LINC00461 was found to promote chondrocyte proliferation and cell cycle progression, and inhibit inflammation and ECM degradation by downregulating miR-30a-5p 42 .…”

Epigenetic Alterations in Sports-Related Injuries

“…It is also worth mentioning that miR-148a-3p promotes thrombospondin-4 expression and enhances angiogenesis during tendinopathy; miR-124 suppresses collagen formation of the human tendon [ 155 ], and miRNA124-3p directly binds and suppresses the expression of early growth response-1 (EGR1) and suppresses the synthesis of collagen during tenogenic differentiation (the transcription factor EGR1 promotes tendon repair and regulates tendon differentiation) [ 149 ]. miR-30b-5p is involved in cartilage degradation in rats with chronic exercise arthritic injury and regulates chondrocyte apoptosis and migration by targeting Hoxa1 [ 156 ]. Age-related cellular dysfunctions have been hypothesised to result in musculoskeletal age-related diseases, such as osteoarthritis, osteoporosis, and tendinopathy.…”

Expressions of bone development related protein BMP5, HMGA1 and PLAG1 varied with the expression of HOXA1 in mouse osteoblasts

“…HOXA1(Homeobox A1) is a member of HOX genes, belongs to the transcription factor family [7,8], which are highly conserved in evolution and are the main control genes of cell proliferation and differentiation, and participate in the growth and development of multiple human systems [9]. Studies have shown that miRNA (mir-18a-3p, mir-30b-5p) could target HOXA1 to regulate chondrocyte apoptosis and migration [10][11][12]. HOXA1 was also known to function in neural crest cell migration, posterior brain pattern, heart and ear development in mice and humans [13].…”