Silencing Hoxa2 reverses dexamethasone-induced dysfunction of MC3T3-E1 osteoblasts and osteoporosis in rats

Abstract

Background.Osteoporosis is damaging the health of women worldwide. Osteoporosis results from the imbalance between bone resorption and formation, which may be regulated by homeobox A2 (Hoxa2). However, the specific role and mechanism of Hoxa2 in osteogenesis and dexamethasone (Dex)-induced osteoporosis remain unknown.Objectives. The present study investigated the effect of Hoxa2 on differentiation and osteoblastogenesis. Materials and methods.Alkaline phosphatase staining and immunofluorescence staining were performed to evaluate the differentiation of MC3T3-E1 cells. Runt-related transcription factor 2 (Runx2), osteoprotegerin (OPG) and receptor activator of nuclear factor-kappa B ligand (RANKL) in Dex stimulated osteoblastic MC3T3-E1 cells, and Dex-induced osteoporotic rats were estimated using western blot and quantitative polymerase chain reaction (qPCR). Serum markers of bone turnover were determined using enzyme-linked immunosorbent assay (ELISA). Trabecular bones of femur tissues were observed using hematoxylin and eosin (H&E) staining.Results. Hoxa2 short hairpin RNA significantly promoted the differentiation of MC3T3-E1 cells and expression of Runx2 and OPG in Dex-treated MC3T3-E1 cells and osteoporotic rats but inhibited the expression of RANKL. Furthermore, silencing Hoxa2 resulted in the upregulation of bone alkaline phosphatase but suppressed the expression of tartrate-resistant acid phosphatase and C-terminal cross-linked telopeptides of type I collagen.Conclusions. Silencing Hoxa2 reversed the Dex-induced inhibition of osteoblastogenesis by modulating Runx2 and RANK-RANKL-OPG axis.

Incorporation of Bone Morphogenetic Protein-2 and Osteoprotegerin in 3D-Printed Ti6Al4V Scaffolds Enhances Osseointegration Under Osteoporotic Conditions

“…The RANKL gene can regulate the differentiation and function of osteoclasts by binding to RANK, which is located on the osteoclast membrane ( Cang et al, 2021 ). The activation of RANK promotes osteoclastic effects and increases bone resorption ( Liu et al, 2021 ). Therefore, the lower expression level of RANKL reveals a lower level of osteoclastic differentiation.…”

The Pathogenic Potential of RUNX2

“…6 The detailed information on Runx2 in the regulation of pathogenicity are summarized in Table 1. [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] Of interest, some factors could influence the expression of Runx2, which include: (1) microRNAs. The deletion of the micro-RNA processing enzyme Dicer leads to decreased expression of miRNAs and Runx2, which suggests a critical role for microRNA in the regulation of Runx2.…”

DataSheet1.PDF

“…The RANKL gene can regulate the differentiation and function of osteoclasts by binding to RANK, which is located on the osteoclast membrane (Cang et al, 2021). The activation of RANK promotes osteoclastic effects and increases bone resorption (Liu et al, 2021). Therefore, the lower expression level of RANKL reveals a lower level of osteoclastic differentiation.…”