Mitochondrial regulation of stem cell osteogenic differentiation: A key driver for bone regeneration

Figure 1 Mitochondria play a crucial role in regulating the osteogenic differentiation of mesenchymal stem cells through various mechanisms, including energy metabolism, oxidative stress regulation, mitochondrial dynamics, and autophagy. ATP: Adenosine triphosphate; OxPhos: Oxidative phosphorylation; TCA: Tricarboxylic acid; NF-κB: Nuclear factor kappa B; ROS: Reactive oxygen species; PI3K: Phosphoinositide 3-kinase; Akt: Protein kinase B; Wnt: Wingless/integrase; MSC: Mesenchymal stem cell; ER: Endoplasmic reticulum; PINK1: PTEN-induced kinase 1.

Figure 2 The strategies for targeting mitochondria in bone regeneration. A: Targeting mitochondrial dynamics, particularly by enhancing functional mitochondrial transfer, can significantly promote bone regeneration potential. For instance, silicified collagen scaffolds significantly improve bone repair outcomes in this way; B: Modulating the level of mitophagy can effectively enhance the osteogenic differentiation capacity of mesenchymal stem cells. For example, WW domain-containing coiled-coil adaptor protein promotes mesenchymal stem cell osteogenesis by activating mitophagy through protecting the key mitophagy initiator. Citation for Figure 2A: Ma YX, Lei C, Ye T, Wan QQ, Wang KY, Zhu YN, Li L, Liu XF, Niu LZ, Tay FR, Mu Z, Jiao K, Niu LN. Silicon Enhances Functional Mitochondrial Transfer to Improve Neurovascularization in Diabetic Bone Regeneration. Adv Sci (Weinh) 2025; 12: E2415459. Copyright© The Authors 2025. Published by Wiley-VCH GmbH. The article is open access (Supplementary material). Citation for Figure 2B: Fan S, Li J, Zheng G, Ma Z, Peng X, Xie Z, Liu W, Yu W, Lin J, Su Z, Xu P, Wang P, Wu Y, Shen H, Ye G. WAC Facilitates Mitophagy-mediated MSC Osteogenesis and New Bone Formation via Protecting PINK1 from Ubiquitination-Dependent Degradation. Adv Sci (Weinh) 2025; 12: E2404107. Copyright© The Authors 2024. Published by Wiley-VCH GmbH. The article is open access (Supplementary material).