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Background <p>Osteoporosis is a prevalent skeletal disorder marked by progressive bone loss and elevated fracture risk, primarily driven by excessive osteoclast-mediated bone resorption. Current therapeutic agents are limited by adverse effects, necessitating the exploration of safer, naturally derived compounds. Myricitrin, a bioactive flavonoid from <i>Myrica rubra</i>, has demonstrated anti-inflammatory and antioxidant properties, but its role in bone metabolism remains underexplored.</p> Objective <p>This study aimed to investigate Myricitrin’s anti-osteoclastic effects and underlying molecular mechanisms using in vitro osteoclast differentiation models and an in vivo ovariectomized (OVX) mouse model of postmenopausal osteoporosis.</p> Methods <p>We evaluated the effects of Myricitrin on osteoclastogenesis in RAW264.7 murine macrophage cells and primary bone marrow-derived macrophages (BMMs). Osteoclast formation was assessed using TRAP staining, and gene and protein expression analyses were performed via qRT-PCR and Western blotting. Immunofluorescence staining was used to visualize the F-actin ring and Vinculin formation. MAPK signaling pathway components (p-ERK, p-JNK, p-p38MAPK) were analyzed, and RNA-sequencing followed by KEGG and GO enrichment assessed transcriptomic changes, particularly in cytokine and chemokine pathways. Using histological and molecular analyses, an OVX-induced osteoporosis model in C57BL/6J mice was employed to evaluate Myricitrin’s protective effects on bone loss.</p> Results <p>Myricitrin significantly inhibited osteoclast differentiation in RAW264.7 and BMMs, as evidenced by reduced TRAP-positive multinucleated cells and downregulation of osteoclast-specific markers, including Acp5, NFAT2, CTSK, and c-fos. It impaired cytoskeletal reorganization by decreasing the F-actin ring and Vinculin expression. Mechanistically, Myricitrin suppressed phosphorylation of key MAPK pathway proteins (ERK1/2, JNK, p38MAPK) in a dose-dependent manner. Transcriptomic analysis revealed altered expression of cytokine and chemokine signaling pathway genes. In vivo, Myricitrin administration dose-dependently mitigated OVX-induced bone loss, reduced osteoclast numbers, and downregulated osteoclast-related protein expression in femoral bone tissue.</p> Conclusions <p>Our findings demonstrate that Myricitrin effectively suppresses osteoclast differentiation through correlative and pharmacological evidences and inhibit the MAPK pathway and modulation of cytokine signaling. The compound also exhibits significant bone-protective effects in OVX mice. These results suggest Myricitrin’s promise as a natural, potential, and multi-targeted therapeutic candidate for osteoporosis treatment.</p>

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Myricitrin as a potent inhibitor of osteoclast differentiation via RAW264.7 Cells, BMMs and ovariectomized mouse model

  • 期刊论文

  • 发表日期：

    2026年7月8日

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  • Jianliang Li,
  • Yanhuai Ma,
  • Jiale Mai,
  • Fanchen Wang,
  • Hao Wang

摘要

Background

Osteoporosis is a prevalent skeletal disorder marked by progressive bone loss and elevated fracture risk, primarily driven by excessive osteoclast-mediated bone resorption. Current therapeutic agents are limited by adverse effects, necessitating the exploration of safer, naturally derived compounds. Myricitrin, a bioactive flavonoid from Myrica rubra, has demonstrated anti-inflammatory and antioxidant properties, but its role in bone metabolism remains underexplored.

Objective

This study aimed to investigate Myricitrin’s anti-osteoclastic effects and underlying molecular mechanisms using in vitro osteoclast differentiation models and an in vivo ovariectomized (OVX) mouse model of postmenopausal osteoporosis.

Methods

We evaluated the effects of Myricitrin on osteoclastogenesis in RAW264.7 murine macrophage cells and primary bone marrow-derived macrophages (BMMs). Osteoclast formation was assessed using TRAP staining, and gene and protein expression analyses were performed via qRT-PCR and Western blotting. Immunofluorescence staining was used to visualize the F-actin ring and Vinculin formation. MAPK signaling pathway components (p-ERK, p-JNK, p-p38MAPK) were analyzed, and RNA-sequencing followed by KEGG and GO enrichment assessed transcriptomic changes, particularly in cytokine and chemokine pathways. Using histological and molecular analyses, an OVX-induced osteoporosis model in C57BL/6J mice was employed to evaluate Myricitrin’s protective effects on bone loss.

Results

Myricitrin significantly inhibited osteoclast differentiation in RAW264.7 and BMMs, as evidenced by reduced TRAP-positive multinucleated cells and downregulation of osteoclast-specific markers, including Acp5, NFAT2, CTSK, and c-fos. It impaired cytoskeletal reorganization by decreasing the F-actin ring and Vinculin expression. Mechanistically, Myricitrin suppressed phosphorylation of key MAPK pathway proteins (ERK1/2, JNK, p38MAPK) in a dose-dependent manner. Transcriptomic analysis revealed altered expression of cytokine and chemokine signaling pathway genes. In vivo, Myricitrin administration dose-dependently mitigated OVX-induced bone loss, reduced osteoclast numbers, and downregulated osteoclast-related protein expression in femoral bone tissue.

Conclusions

Our findings demonstrate that Myricitrin effectively suppresses osteoclast differentiation through correlative and pharmacological evidences and inhibit the MAPK pathway and modulation of cytokine signaling. The compound also exhibits significant bone-protective effects in OVX mice. These results suggest Myricitrin’s promise as a natural, potential, and multi-targeted therapeutic candidate for osteoporosis treatment.