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Peer-reviewedCC BY 4.0Frontiers in Endocrinology

Bidirectional mitochondrial transfer in the osteoimmune microenvironment: mechanisms and therapeutic perspectives

  • Lei Huang1,2,3
  • Xin Chen1,2
  • Yuqin Guo1,2
  • Fang Guo1,2
  • Yanfan Zhang4
  • Xuanyi Li1,2,3
  • Zhili Dong1,2
  • Xiaoxing Kou1,2,3
4 affiliations
  1. 1Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University
  2. 2Guangdong Provincial Key Laboratory of Stomatology
  3. 3South China Center of Craniofacial Stem Cell Research, Guanghua School of Stomatology, Sun Yat-sen University
  4. 4Department of Temporomandibular Joint, School and Hospital of Stomatology, Guangzhou Medical University
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Abstract

The maintenance of bone homeostasis relies on a dynamic interplay between skeletal and immune cells. Traditional paracrine and receptor-based models cannot fully explain the reciprocal communication that underpins bone remodeling. Intercellular mitochondrial transfer refers to the movement of one or more mitochondria from a donor cell to a recipient cell. In this review, this term is distinguished from the intercellular transfer of mitochondrial components, which is described separately according to the nature of the transferred material. Mitochondrial transfer occurs via three primary pathways: direct contact, extracellular vesicles (EVs), and free mitochondrial release. Emerging evidence positions intercellular mitochondrial transfer as a novel form of organelle-level communication in the regulation of bone homeostasis. Although mitochondrial transfer has been documented extensively in bone-related pathologies, its context-dependent, bidirectional regulatory roles within the osteoimmune microenvironment have yet to be systematically elucidated. To address this gap, we systematically summarize the molecular mechanisms governing mitochondrial transfer within the osteoimmune microenvironment, with a particular emphasis on the bidirectional communication network between skeletal cells and immune cells. We further discuss its dual pathophysiological roles in bone-related disorders and highlight emerging therapeutic strategies based on mitochondrial transfer. We also propose a novel framework for bone remodeling interventions that centers on precise control of both transfer directionality and mitochondrial quality. This conceptual integration provides a theoretical foundation and translational guidance for precision regenerative medicine and immunometabolic therapies in bone-related diseases.

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Cite

BibTeXRIS
BibTeX
@article{huang2026bidirectional,
  title = {{Bidirectional mitochondrial transfer in the osteoimmune microenvironment: mechanisms and therapeutic perspectives}},
  author = {Lei Huang and Xin Chen and Yuqin Guo and Fang Guo and Yanfan Zhang and Xuanyi Li and Zhili Dong and Xiaoxing Kou},
  journal = {Frontiers in Endocrinology},
  year = {2026},
  month = oct,
  doi = {10.3389/fendo.2026.1978936},
  url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1978936/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Bidirectional mitochondrial transfer in the osteoimmune microenvironment: mechanisms and therapeutic perspectives
AU  - Lei Huang
AU  - Xin Chen
AU  - Yuqin Guo
AU  - Fang Guo
AU  - Yanfan Zhang
AU  - Xuanyi Li
AU  - Zhili Dong
AU  - Xiaoxing Kou
PY  - 2026
DA  - 2026/10/19
JO  - Frontiers in Endocrinology
DO  - 10.3389/fendo.2026.1978936
UR  - https://www.frontiersin.org/articles/10.3389/fendo.2026.1978936/full
AB  - The maintenance of bone homeostasis relies on a dynamic interplay between skeletal and immune cells. Traditional paracrine and receptor-based models cannot fully explain the reciprocal communication that underpins bone remodeling. Intercellular mitochondrial transfer refers to the movement of one or more mitochondria from a donor cell to a recipient cell. In this review, this term is distinguished from the intercellular transfer of mitochondrial components, which is described separately according to the nature of the transferred material. Mitochondrial transfer occurs via three primary pathways: direct contact, extracellular vesicles (EVs), and free mitochondrial release. Emerging evidence positions intercellular mitochondrial transfer as a novel form of organelle-level communication in the regulation of bone homeostasis. Although mitochondrial transfer has been documented extensively in bone-related pathologies, its context-dependent, bidirectional regulatory roles within the osteoimmune microenvironment have yet to be systematically elucidated. To address this gap, we systematically summarize the molecular mechanisms governing mitochondrial transfer within the osteoimmune microenvironment, with a particular emphasis on the bidirectional communication network between skeletal cells and immune cells. We further discuss its dual pathophysiological roles in bone-related disorders and highlight emerging therapeutic strategies based on mitochondrial transfer. We also propose a novel framework for bone remodeling interventions that centers on precise control of both transfer directionality and mitochondrial quality. This conceptual integration provides a theoretical foundation and translational guidance for precision regenerative medicine and immunometabolic therapies in bone-related diseases.
SN  - 1664-2392
ER  -