2. Academic Validation
  3. Mitochondria serve as a source of mineral precursors initiating early cartilage calcification in osteoarthritis

Mitochondria serve as a source of mineral precursors initiating early cartilage calcification in osteoarthritis

  • Sci Bull (Beijing). 2026 May 15;71(9):2300-2315. doi: 10.1016/j.scib.2026.02.044.
Qianqian Wan 1,  Tao Ye 2,  Junting Gu 2,  Yuxuan Ma 2,  Wen Qin 2,  Jianfei Yan 2,  Jin Rao 2,  Lei Chen 2,  Dongxiao Hao 2,  Franklin R Tay 3,  Kai Jiao 4,  Lina Niu 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China; Department of Stomatology, Air Force Medical Center, Beijing 100142, China.
  • 2 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
  • 3 The Graduate School, Augusta University, Augusta, GA 30912, USA.
  • 4 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China; Department of Stomatology, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710032, China. Electronic address: [email protected].
  • 5 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China. Electronic address: [email protected].
PMID: 41864783 DOI: 10.1016/j.scib.2026.02.044
Abstract

Cartilage calcification actively contributes to osteoarthritis progression by generating mineral depositions that disrupt joint homeostasis and amplify matrix degradation. Previous studies found that chondrocyte-derived matrix vesicles provide the Minerals orchestrating pathological cartilage calcification. However, the intracellular origin of Minerals in osteoarthritic cartilage remains elusive, significantly impeding the development of targeted therapies. This study identified mitochondria as subcellular reservoirs of mineral precursors containing calcium and phosphorus. At the early stage of osteoarthritis, chondrocyte mitochondrial DNA (mtDNA) is transformed into an intertwined state that enables them to stabilize Minerals into amorphous precursors. The stabilized amorphous mineral precursors are then transported via vesicles to the mineralization site. Targeting mtDNA distribution by modulating coiled-coil-helix, coiled-coil-helix-domain containing 6 (CHCHD6) can inhibit cartilage calcification and impair osteoarthritis progression. Our findings provide mechanistic insights into mitochondrial orchestration of incipient pathological cartilage calcification in osteoarthritis. Elucidating the mitochondrial-driven calcification cascade redefines therapeutic paradigms, enabling rational design of mineralization-inhibitory strategies for early management of osteoarthritis.

Keywords

Early treatment; Mineral precursors; Osteoarthritis; Pathological calcification; mtDNA aggregation.

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