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Updated: Jul 2, 2025

A Simple Pit Assay Protocol to Visualize and Quantify Osteoclastic Resorption In Vitro
Published on: June 16, 2022
Basic-helix-loop-helix family member e41 suppresses osteoclastogenesis and abnormal bone resorption disease via
Yufeng Zhang1, Xiaoguang Li1, Jianlong Lang1
1Department of Orthopedics, The Second Hospital of Tianjin Medical University, Tianjin 300211, China.
Abstract:
Overactivation of osteoclasts due to altered osteoclastogenesis causes multiple bone metabolic diseases. However, how osteoclast differentiation is tightly regulated and involved in multiple pathophysiological states remains mystery. In this study, we noticed that the downregulation of BHLHE41 (basic-helix-loop-helix family member e41) was tightly associated with osteoclast differentiation and osteoporosis. Functionally, the upregulation or downregulation of BHLHE41 suppressed or promoted osteoclast differentiation, respectively, in vitro. A mechanism study indicated that the direct binding of BHLHE41 to the promoter region of NFATc1 that led to its downregulation. Notably, the inhibition of NFATc1 abrogated the enhanced osteoclast differentiation in BHLHE41-knockdown bone marrow macrophages (BMMs). Additionally, upregulation of BHLHE41 impeded bone destruction in OVX mice with osteoporosis. Therefore, our research reveals the mechanism by which BHLHE41 regulates osteoclast differentiation and bone resorption via NFATc1, and targeting BHLHE41 is a potential strategy for the treatment of osteoporosis.
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