Abstract
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. The present study investigated the effect of Hoxa2 on differentiation and osteoblastogenesis. 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. 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. Silencing Hoxa2 reversed the Dex-induced inhibition of osteoblastogenesis by modulating Runx2 and RANK-RANKL-OPG axis.
Highlights
Osteoporosis is damaging the health of women worldwide
The present study investigated the effect of Hoxa[2] on differentiation and osteoblastogenesis
The precise balance of bone turnover depends on the homeostasis of osteoblast-mediated bone formation and osteoclast-mediated bone resorption, which are mediated by a multitude of critical molecules working through various signaling pathways.[1]
Summary
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 (Hoxa[2]). The proliferation and differentiation of osteoblasts from undifferentiated mesenchymal cells play important roles in bone formation.[2] Glucocorticoid-induced osteoporosis is regarded as the most common form of secondary osteoporosis and involves a reduction in osteoblastogenesis[3]; Dex-treated osteoblast and animal models have been widely accepted as in vitro and in vivo models of osteoporosis.[4,5] osteoporosis treatments based on the inhibition of bone resorption and promotion of bone formation are widely used, prolonged administration of these agents, such as bisphosphonates or estrogen receptor modulator, can lead to several adverse effects such as mandibular necrosis, venous thrombosis, cardiac arrhythmia, and renal inadequacy.[6] more effective therapeutic strategies with fewer adverse reactions are urgently needed. There is still considerable need for illustrating the effects of critical regulatory factors of osteoblastogenesis and for therapeutic targets associated with osteoporosis
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