Silence of lncRNA BCAR4 alleviates the deterioration of osteoporosis.

Abstract

To illustrate the biological function of long non-coding RNA (lncRNA) BCAR4 in triggering osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), thus mediating the progression of osteoporosis. Relative levels of BCAR4 in BMSCs undergoing indicated time points of osteogenic differentiation were examined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). After intervening BCAR4 levels in osteogenically differentiated BMSCs, the relative levels of serum osteocalcin (OCN) and osteopontin (OPN) were detected, as well as ALP activity and mineralization capacity. Female Sprague Dawley (SD) rats were classified into sham group, BMSCs group (administration with BMSCs), RNAi group (administration with BMSCs transfected with si-BCAR4), and control group, with 10 rats per group. Osteoporosis model was generated in the latter three groups by resection of bilateral ovaries. Positive expressions of procollagen type I N propeptide (PINP) and β-C-terminal telopeptide (β-CTx), and β-CTx in rats were determined by enzyme-linked immunosorbent assay (ELISA). Bone density in rat femurs and bone biomechanics were examined using the dual energy X-ray bone densitometer and the three-point bending test, respectively. BCAR4 was downregulated on the 3rd and 7th day of osteogenic differentiation in BMSCs. Overexpression of BCAR4 downregulated OCN and OPN. In the meantime, BCAR4 was able to weaken alkaline phosphatase (ALP) activity and mineralization capacity in BMSCs. The promotive effects of silenced BCAR4 on osteogenic potentials in BMSCs were abolished by overexpression of GLI2. In rats of RNAi group, positive expression of PINP and bone biomechanics were remarkably higher than BMSCs group, whereas they were lower than the sham group. Positive expression of β-CTx was declined in RNAi group compared with that of BMSCs group, and it was still higher than that of sham group. BCAR4 is involved in the osteogenic differentiation of BMSCs. The knockdown of BCAR4 can alleviate the progression of osteoporosis.