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<p>Orthodontically induced inflammatory root resorption (OIIRR) is a prevalent complication driven by excessive mechanical force, yet the underlying mechanisms linking mechanotransduction to osteoclast activation remain elusive. Here, we identify a novel signaling axis wherein sphingosine kinase 1 (SphK1) in cementocytes translates heavy orthodontic force into a pro-osteoclastogenic signal via mitophagy-mediated mitochondrial transfer. In vivo, heavy force induced OIIRR and upregulated mitophagy markers in cementocytes. In vitro, heavy compression force triggered SphK1-dependent mitophagy in IDG-CM6 cementocytes, as evidenced by increased mitophagosome formation, co-localization of mitochondria with lysosomes, and elevated PINK1/PARKIN signaling. Inhibition of SphK1, either pharmacologically or genetically, suppressed this mitophagic response. Conditioned media from force-loaded cementocytes enhanced osteoclast differentiation and glycolytic metabolism, effects that were abolished by SphK1 inhibition and rescued by a mitophagy agonist. Crucially, we demonstrated that heavy force promotes the transfer of mitochondria from cementocytes to osteoclast precursors, a process dependent on mitophagy. This transferred mitochondrial cargo functioned as a metabolic subsidy, boosting osteoclast bioenergetics and resorptive activity. Our findings unveil the SphK1-mitophagy-mitochondrial transfer axis as a fundamental mechanism of cementocyte-osteoclast communication, positioning SphK1 as a promising therapeutic target to prevent OIIRR.</p>

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SphK1/mitophagy axis in cementocytes drives orthodontic root resorption via mitochondrial transfer to osteoclasts

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月14日

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  • Han Wang,
  • Sihang Chen,
  • Shuo Chen,
  • Chengchen Duan,
  • Li Zhu,
  • Hengyi Lin,
  • Shujuan Zou,
  • Yu Li,
  • Peipei Duan

摘要

Orthodontically induced inflammatory root resorption (OIIRR) is a prevalent complication driven by excessive mechanical force, yet the underlying mechanisms linking mechanotransduction to osteoclast activation remain elusive. Here, we identify a novel signaling axis wherein sphingosine kinase 1 (SphK1) in cementocytes translates heavy orthodontic force into a pro-osteoclastogenic signal via mitophagy-mediated mitochondrial transfer. In vivo, heavy force induced OIIRR and upregulated mitophagy markers in cementocytes. In vitro, heavy compression force triggered SphK1-dependent mitophagy in IDG-CM6 cementocytes, as evidenced by increased mitophagosome formation, co-localization of mitochondria with lysosomes, and elevated PINK1/PARKIN signaling. Inhibition of SphK1, either pharmacologically or genetically, suppressed this mitophagic response. Conditioned media from force-loaded cementocytes enhanced osteoclast differentiation and glycolytic metabolism, effects that were abolished by SphK1 inhibition and rescued by a mitophagy agonist. Crucially, we demonstrated that heavy force promotes the transfer of mitochondria from cementocytes to osteoclast precursors, a process dependent on mitophagy. This transferred mitochondrial cargo functioned as a metabolic subsidy, boosting osteoclast bioenergetics and resorptive activity. Our findings unveil the SphK1-mitophagy-mitochondrial transfer axis as a fundamental mechanism of cementocyte-osteoclast communication, positioning SphK1 as a promising therapeutic target to prevent OIIRR.