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<p>Curcuminoids, the major bioactive compounds in <i>Curcuma longa</i> L., inhibit osteoclast differentiation—a key process in bone resorption. microRNA-223 regulates osteoclast differentiation by targeting nuclear factor I-A. How curcuminoids influence osteoclast differentiation through microRNA-223 is unclear. This study investigated the effects of CRE-Bin—a binary curcuminoid complex of a curcuminoid-rich extract and hydroxypropyl-β-cyclodextrin—on osteoclast differentiation. In murine receptor activator of nuclear factor-κB ligand-stimulated RAW 264.7 macrophages, CRE-Bin inhibited osteoclast differentiation and bone resorption by reducing tartrate-resistant acid phosphatase activity, cathepsin K expression, reactive oxygen species production, and canonical NF-κB signaling pathway. CRE-Bin suppressed microRNA-223 expression at the primary, precursor, and mature stages while upregulating nuclear factor I-A expression, suggesting dual regulatory effects. Molecular docking simulations demonstrated strong interactions between microRNA-223 and the IκBα/p50/p65 complex, indicating crosstalk between microRNA-223 and canonical NF-κB signaling pathway. Binding affinity predictions revealed moderate interactions between curcuminoids and mature microRNA-223, underscoring their potential for microRNA-targeted modulation. These findings position CRE-Bin as a promising multitarget therapeutic agent for bone-related disorders and diseases, warranting experimental and computational investigations.</p>

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Binary curcuminoid complex CRE-Bin inhibits osteoclast differentiation by suppressing the canonical NF-κB signaling pathway and modulating microRNA-223 expression

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月1日

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  • Sompot Jantarawong,
  • Wipapan Khimmaktong,
  • Piyawut Swangphon,
  • Natda Lauterbach,
  • Natthaphon Nanakorn,
  • Pharkphoom Panichayupakaranant,
  • Yutthana Pengjam

摘要

Curcuminoids, the major bioactive compounds in Curcuma longa L., inhibit osteoclast differentiation—a key process in bone resorption. microRNA-223 regulates osteoclast differentiation by targeting nuclear factor I-A. How curcuminoids influence osteoclast differentiation through microRNA-223 is unclear. This study investigated the effects of CRE-Bin—a binary curcuminoid complex of a curcuminoid-rich extract and hydroxypropyl-β-cyclodextrin—on osteoclast differentiation. In murine receptor activator of nuclear factor-κB ligand-stimulated RAW 264.7 macrophages, CRE-Bin inhibited osteoclast differentiation and bone resorption by reducing tartrate-resistant acid phosphatase activity, cathepsin K expression, reactive oxygen species production, and canonical NF-κB signaling pathway. CRE-Bin suppressed microRNA-223 expression at the primary, precursor, and mature stages while upregulating nuclear factor I-A expression, suggesting dual regulatory effects. Molecular docking simulations demonstrated strong interactions between microRNA-223 and the IκBα/p50/p65 complex, indicating crosstalk between microRNA-223 and canonical NF-κB signaling pathway. Binding affinity predictions revealed moderate interactions between curcuminoids and mature microRNA-223, underscoring their potential for microRNA-targeted modulation. These findings position CRE-Bin as a promising multitarget therapeutic agent for bone-related disorders and diseases, warranting experimental and computational investigations.