Histone H3K4 monomethyltransferase SETD7 promoted osteogenic differentiation of bone marrow mesenchymal stem cells exposed to Hydroquinone via autophagy.

Hydroquinone (HQ), a major metabolite of benzene, is a recognized risk factor for acute myeloid leukemia (AML). However, the mechanisms underlying HQ-associated leukaemogenesis remain incompletely understood. Increasing evidence suggests that defective osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), contributes to HQ-induced hematopoietic dysfunction and leukemic progression. SET domain-containing 7 (SETD7) has been found to regulate the proliferation and differentiation of BMSCs, while autophagy is known to play a crucial role in promoting osteogenic differentiation. Therefore, this study aimed to investigate the regulatory roles of SETD7 and autophagy in the osteogenic differentiation of HQ-exposed BMSCs. The results demonstrated that HQ exposure was associated with decreased histone 3 lysine 4 monomethylation (H3K4me1) and SETD7 protein levels, autophagy, and osteogenic differentiation capacity in BMSCs. Activation of autophagy by rapamycin (Rapa) effectively rescued the BMSCs osteogenic differentiation reduced by HQ. Moreover, overexpression of SETD7 restored both autophagic activity and osteogenic differentiation capacity suppressed by HQ. Notably, co-treatment with the autophagy inhibitor 3-methyladenine (3-MA) abrogated the pro-osteogenic effects induced by SETD7 overexpression in HQ-exposed BMSCs. Collectively, these findings indicated that SETD7 promoted osteogenic differentiation in HQ-exposed BMSCs via autophagy-dependent mechanism. This study provides mechanistic insight into how HQ may disrupt the bone marrow microenvironment, highlights the role of SETD7 in maintaining osteogenic differentiation and autophagy in HQ-exposed BMSCs, and contributes to a better understanding of the epigenetic and cellular pathways involved in HQ-induced hematotoxicity.