MicroRNA-218 promotes early chondrogenesis of mesenchymal stem cells and inhibits later chondrocyte maturation

Abstract

BackgroundMicroRNAs (miRNAs) reportedly participate in the mesenchymal stem cell (MSC) chondrogenic differentiation regulation. We objected to examine how miR-218 regulate chondrogenic differentiation of synovium-derived MSCs (SDSCs) and the maturation of RCJ3.1C5.1 chondrocytes. SDSCs were sourced from the knee joint synovium of New Zealand white rabbits, and their multilineage differentiation potentials were examined. The level of miR-218 was measured during SDSC chondrogenic differentiation, together with determination of SDSCs chondrogenic markers and RCJ3.1C5.1 chondrocytes maturation markers expression level after transfection of miR-218 mimics/inhibitor.ResultsmiR-218 expression was notably upregulated in early chondrogenesis but mostly ceased during the maturation phases of chondrogenic differentiation in SDSCs. The transfection of miR-218 mimics notably enhanced SDSCs chondrocytes differentiation, as evidenced by augmented expressions of chondrogenic markers (SOX9, COL2A1, ACAN, GAG, and COMP) in terms of mRNA and protein level, and the inhibition of miR-218 yielded opposite resutls. Additionally, miR-218 overexpression substantially suppressed the expression of osteogenic markers (ALP, BSP, COL1A1, OCN and OPN) during the early stage of chondrogenesis while increasing that of chondrogenic markers (SOX9, COL2A1, ACAN, GAG and COMP). However, miR-218 mimics notably suppressed maturation markers (CMP, COL10A1, MMP-13 and VEGF) expression in RCJ3.1C5.18 chondrocytes, and the miR-218 inhibitor promoted the expression of these maturation markers. We proposed miR-218 plays a regulatory role on 15-hydroxyprostaglandin dehydrogenase (HPGD), which plays a key role in chondrogenic differentiation, and this finding indicates that miR-218 directly regulates HPGD expression in SDSCs.ConclusionOur study suggests that miR-218 contributes to early chondrogenesis while suppressing later chondrocyte maturation. The miR-218-HPGD pathway offers us a perspective into how SDSCs differentiate into chondrogenic cells.

MicroRNA-27b targets CBFB to inhibit differentiation of human bone marrow mesenchymal stem cells into hypertrophic chondrocytes

“…Accumulating evidence has shown that a number of miRNAs, including miR-140, miR-143, miR-145, miR-483, miR-181a, miR-218, and miR-410, play critical roles in hBMSC chondrogenic differentiation [15,23,25,40,44,45]. The miR-140, miR-143, miR-145, miR-181a, and miR-221 expression patterns during hBMSC chondrogenic differentiation in our conditions were in line with those reported in previous studies [15].…”

“…Overexpression of miR-145 in C3H10T1/2 cells reduced SOX9 expression, thus significantly suppressing cartilage matrix synthesis in vitro [20]. Additionally, miR-495, miR-92a, miR-483, miR-892b, and miR-218 have been found to play important roles in hBMSC chondrogenic differentiation [21][22][23][24][25]. Whether other miRNAs are involved in this process has not yet been clearly elucidated.…”

miR-152 Attenuates Apoptosis in Chondrocytes and Degeneration of Cartilages in Osteoarthritis Rats via TCF-4 Pathway

“… 20 Multiple studies have reported involvement of miRs in the pathogenesis of osteoarthritis such as miR-218, miR-365, miR-145 and miR-146a. 6 , 8 - 10 miR-152-3p is over-expressed in postmenopausal females reported with osteoporosis and fracture, fragile suggesting a link between miR-152 and osteoporosis affecting the osteoblasts differentiation. 12 miR-152 exerts inhibitory effect on the levels of cytokines like IL-12, IL-6 and the TNF-α, 13 in addition to this miR-152 blocks the expression of pro-inflammatory cytokines in Rheumatoid arthritis.…”

“… 5 - 7 miR-218 has been reported to promote the process of chondrogenesis of mesenchymal stem cells and also inhibited the later chondrocyte maturation by involving the HPGD pathway. 8 miR-365 has been found to target histone deacetylase- 4 and increases the process of chondrogenesis. 9 miR-145 have been reported to regulate the differentiation of chondrocytes in stem cells via the SOX9 pathway.…”

Scaffold-Based Gene Therapeutics for Osteochondral Tissue Engineering

“…Carriers have been employed to deliver miRNA-149-5p to MSCs to promote chondrogenesis (Celik et al, 2019). MiR-218 is highly expressed early in cartilage formation, but is stopped in synaptic-derived mesenchymal stem cells (SDSC) at the maturation stage of cartilage differentiation and miR-218 may directly regulates 15hydroxyprostaglandin dehydrogenase expression in SDSCs (Chen et al, 2019c). MiR-320c was decreased in the later stages of chondrogenesis of adipose-derived stem cells (hADSCs) and OA chondrocytes.…”