Journal of Orthopaedic Surgery and Research· 2026Q1
Teriparatid Travma ve İskemi Sonrası Kemik Kaybını Önler
Teriparatide alleviates limb ischemia-associated posttraumatic bone loss: potential involvement of the AKT/HIF-1α/VEGFA signaling axis
- 0atıf
- Q1SCImago
- 2026yıl
Kısa özet
Teriparatid (TPTD) tedavisi (40 µg/kg), travma sonrası kemik kaybını artıran bir durum olan femoral arter ligasyonu ile birlikte kırık modelinde kemik kaybını önemli ölçüde azaltmış ve kemik mikro yapısını iyileştirmiştir.
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Ana noktalar
- Femoral arter ligasyonunun eşlik ettiği durumlar, femoral kırık sonrası kemik kaybını ve mikro yapısal bozulmayı şiddetlendirmiştir.
- Aralıklı TPTD (40 µg/kg) tedavisi, kompozit modelde kırık iyileşmesini teşvik etmiş ve ikincil kemik kaybını azaltmıştır.
- TPTD (1 nM), MC3T3-E1 hücrelerinde hipoksi kaynaklı osteojenik farklılaşma baskısını hafifletmiştir.
- TPTD, AKT fosforilasyonunu, HIF-1α nükleer birikimini ve VEGFA ekspresyonunu artırmıştır; bu etkiler AKT inhibitörü LY294002 tarafından engellenmiştir.
Yapay zekâ ile başlık ve abstract'tan üretildi; tam metin okunmaz.
Özet (abstract)
Posttraumatic bone loss is a common clinical complication characterized by localized osteopenia and microstructural degradation after traumatic injury. However, its precise pathogenesis remains unclear. Teriparatide (TPTD), administered intermittently, exerts potent pro-osteogenic and pro-angiogenic effects, and is widely used in the treatment of primary osteoporosis. This study aimed to investigate the therapeutic efficacy of TPTD in mitigating ischemia-associated posttraumatic bone loss, as well as to investigate the underlying molecular mechanisms. In vivo, models of simple femoral fracture and fracture with ipsilateral femoral artery ligation were established to evaluate secondary bone loss associated with arterial ligation, and the therapeutic efficacy of intermittent TPTD was subsequently assessed. In vitro, chemical hypoxia was induced in MC3T3-E1 cells using CoCl 2 . Intermittent TPTD was applied to both models. Furthermore, the inhibitor LY294002 was used in vitro to assess the involvement of the AKT/HIF-1α/VEGFA pathway. In vivo, compared with femoral fracture alone, concurrent femoral artery ligation markedly exacerbated bone loss and microarchitectural deterioration in the ipsilateral tibial metaphysis, characterized by decreased BMD and BV/TV, as well as increased osteoclast numbers. In this composite model, intermittent TPTD (40 µg/kg) not only promoted fracture healing but also attenuated secondary bone loss, restoring bone microarchitecture and angiogenesis-related markers. In vitro, intermittent TPTD (1 nM) significantly alleviated CoCl 2 -induced suppression of osteogenic differentiation in MC3T3-E1 cells. Mechanistically, TPTD promoted AKT phosphorylation, enhanced HIF-1α nuclear accumulation, and upregulated VEGFA, thereby enhancing pro-angiogenic paracrine activity. Notably, these osteogenic and pro-angiogenic effects were markedly attenuated by the PI3K/AKT inhibitor LY294002. In vivo and in vitro studies suggest that TPTD may have therapeutic potential for ischemia-associated posttraumatic bone loss. Mechanistically, the AKT/HIF-1α/VEGFA signaling axis may contribute, at least in part, to the osteogenic and pro-angiogenic effects of TPTD.
Yazarların özeti; kaynağından alınmıştır. Journal of Orthopaedic Surgery and Research, 2026 · DOI ↗
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Alan: Romatoloji
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