HOXA7 Impairs Osteogenic Differentiation via p38/JNK Signaling: Implications for Osteoporosis.

OBJECTIVE

To elucidate the role and mechanism of HOXA7 in osteoporosis (OP), with the goal of informing future research directions in OP.

METHODS

We assessed HOXA7 gene and protein expression; the effect of HOXA7 on osteogenic differentiation in human bone marrow-derived mesenchymal stem cells (hBMSCs); and proliferation, apoptosis, and autophagy in MC3T3-E1 cells. We also evaluated p38 MAPK/JNK pathway-associated proteins in hBMSCs and MC3T3-E1 cells. Cells were transfected with si-HOXA7 and cultured with or without the JNK inhibitor SP600125 or the p38 inhibitor SB203580, after which cell viability, apoptosis, and autophagy were re-assessed.

RESULTS

HOXA7 overexpression inhibited osteogenic differentiation of hBMSCs, reduced OPG, OPN, and RUNX2 expression in hBMSCs, and decreased proliferation while promoting apoptosis in MC3T3-E1 cells. In vitro, HOXA7 modulated autophagy markers in MC3T3-E1 cells. Phosphorylated JNK and p38 (p-JNK, p-p38) were increased in hBMSCs following osteogenic induction, whereas HOXA7 upregulation significantly suppressed p-JNK and p-p38 in MC3T3-E1 cells. SP600125 and SB203580 attenuated the effects of HOXA7 silencing on proliferation, apoptosis, and autophagy in MC3T3-E1 cells.

CONCLUSION

HOXA7 reduces osteogenesis and osteoblast proliferation and promotes osteoblast apoptosis via the p38 MAPK/JNK pathway, suggesting potential therapeutic avenues against OP.