Science China Life Sciences · Mar 28, 2026

KLF6 regulates osteoclastogenesis through DUSP16 in OVX-induced bone loss

By Yang C, Zhang W, Liu X et al.

Estrogen deficiency results in enhanced bone resorption by osteoclasts, a critical factor in the development of postmenopausal osteoporosis. This study investigates the regulatory role of KLF6 in osteoclast differentiation and evaluates its potential in reducing bone loss in ovariectomized (OVX) mice. The results show that the expression of KLF6 gradually decreases during osteoclast differentiation, and this decrease is more pronounced in the OVX model. Reducing the expression level of KLF6 can promote the differentiation of osteoclasts. Through RNA sequencing and ChIP analysis, we found that KLF6 inhibits the activity of the MAPK signaling pathway by upregulating the expression of DUSP16, thereby suppressing osteoclast differentiation. In vivo experiments demonstrate that overexpression of KLF6 via adeno-associated virus can reduce OVX-induced bone loss, suggesting that KLF6 may serve as a potential therapeutic target for bone loss caused by estrogen deficiency.

doi.org/10.1007/s11427-025-3219-4 PubMed 42258131 Interventions