Bindarit Reduces Bone Loss in Ovariectomized Mice by Inhibiting CCL2 and CCL7 Expression via the NF-κB Signaling...

Area of Science:

• Immunology
• Endocrinology
• Pharmacology

Background:

• Postmenopausal osteoporosis (PMOP) is associated with increased proinflammatory cytokines and chemokines.
• C-C motif ligand (CCL) 2 and CCL7 are implicated in the pathogenesis of PMOP.

Purpose of the Study:

• To investigate the role of CCL2 and CCL7 in PMOP.
• To evaluate bindarit (Bnd), a novel inhibitor of CCL2 and CCL7, as a potential therapeutic agent for PMOP using an ovariectomized (OVX) mouse model.

Main Methods:

• RNA sequencing of bone marrow macrophages (BMMs) from women with and without PMOP.
• In vitro differentiation of BMMs into osteoclasts and osteoblasts, treated with Bnd or 17 beta estradiol (E2).
• In vivo studies using OVX mice treated with Bnd or E2, assessing bone parameters, osteoclastogenesis, osteogenesis, and the NF-κB signaling pathway.

Main Results:

• CCL2, CCL7, CCR2, and the NF-κB pathway were elevated in women with PMOP.
• Bnd and E2 treatment reduced osteoclastogenesis, CCL2/CCL7 expression, and bone loss in OVX mice.
• Bnd inhibited NF-κB signaling in BMMs and reduced bone turnover in vivo without directly affecting osteoblast mineralization.

Conclusions:

• CCL2, CCL7, and CCR2 are correlated with PMOP.
• Bindarit (Bnd) attenuates CCL2 and CCL7 levels, mitigating osteoporosis in OVX mice via the NF-κB pathway.
• Bnd demonstrates potential as a novel therapeutic for preventing PMOP.