Functional matrix vesicle replacement partially restores chemo-mechanical coupling in the aged bone niche.

Liqiang Zhang, Xiao Wei, Ke Zhang, Fan Ding, Ziliang Guo, Bin Zou, Wangxiao He, Wenjia Liu

Department of Stomatology, Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; Institute for Stem Cell & Regenerative Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.Department of Stomatology, Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; Institute for Stem Cell & Regenerative Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China. · pubmed

Paper

Abstract

Skeletal aging involves pyrophosphate/phosphate disequilibrium and impaired mechanotransduction, which together constrain osteogenic repair. We develop OsteoVes, a matrix-vesicle-mimetic extracellular organelle that combines tissue-nonspecific alkaline phosphatase (ALP)-mediated inorganic pyrophosphate (PPi) hydrolysis, nano-hydroxyapatite nucleation, and a mesenchymal stem cell-derived membrane interface for extracellular matrix anchoring. In aged human mesenchymal stem/stromal cells (MSCs), OsteoVes restores the Pi/PPi set point, suppresses PPARG activity, promotes RUNX2 nuclear translocation, and supports osteogenic differentiation. OsteoVes also increases actomyosin tension and engages an ITG/FAK-PIEZO1-JNK/c-JUN-RUNX2 mechanotransduction-associated pathway. In elderly osteopenic/osteoporotic patient-derived MSCs, OsteoVes supports ALP activity and matrix mineralization. Systemic administration improves trabecular microarchitecture and mechanical properties in naturally aged mice within 4 weeks, remains active in Alpl

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Research summary

OsteoVes restores chemo-mechanical coupling in aged bone by regulating the Pi/PPi balance and mechanotransduction pathways. This represents an incremental therapeutic advance for age-related bone loss rather than a fundamental solution to the root causes of aging.

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