Kaback Lee A, Soung Do Y, Naik Amish, Geneau Graziello, Schwarz Edward M, Rosier Randy N, O'Keefe Regis J, Drissi Hicham
The Center for Musculoskeletal Research, University of Rochester, Rochester, New York, USA.
J Cell Biochem. 2008 Sep 1;105(1):219-26. doi: 10.1002/jcb.21816.
Based on remarkable success of PTH as an anabolic drug for osteoporosis, case reports of off-label use of teriparatide (1-34 PTH) in patients with complicated fractures and non-unions are emerging. We investigated the mechanisms underlying PTH accelerated fracture repair. Bone marrow cells from 7 days 40 microg/kg of teriparatide treated or saline control mice were cultured and Osx and osteoblast phenotypic gene expression assessed by real-time RT-PCR in these cells. Fractured animals injected daily with either saline or 40 microg/kg of teriparatide for up to 21 days were X-rayed and histological assessment performed, as well as immunohistochemical analyses of the Osx expression in the fracture callus. Osx, Runx2 and osteoblast or chondrocyte phenotypic gene expression was also assessed in fracture calluses. Our data shows that Osx and Runx2 are up-regulated in marrow-derived MSCs isolated from mice systemically treated with teriparatide. Furthermore, these MSCs undergo accelerated osteoblast maturation compared to saline injected controls. Systemic teriparatide treatments also accelerated fracture healing in these mice concomitantly with increased Osx expression in the PTH treated fracture calluses compared to controls. Collectively, these data suggest a mechanism for teriparatide mediated fracture healing possibly via Osx induction in MSCs.
基于甲状旁腺激素（PTH）作为治疗骨质疏松症的合成代谢药物取得的显著成功，关于特立帕肽（1-34 PTH）在复杂骨折和骨不连患者中进行非标签使用的病例报告不断涌现。我们研究了PTH加速骨折修复的潜在机制。对经40微克/千克特立帕肽处理7天的小鼠或生理盐水对照小鼠的骨髓细胞进行培养，并通过实时逆转录聚合酶链反应（RT-PCR）评估这些细胞中Osx和成骨细胞表型基因的表达。对每天注射生理盐水或40微克/千克特立帕肽长达21天的骨折动物进行X线检查和组织学评估，并对骨折痂中的Osx表达进行免疫组织化学分析。还对骨折痂中的Osx、Runx2以及成骨细胞或软骨细胞表型基因表达进行了评估。我们的数据表明，从经特立帕肽全身治疗的小鼠分离出的骨髓间充质干细胞（MSCs）中，Osx和Runx2上调。此外，与注射生理盐水的对照组相比，这些MSCs的成骨细胞成熟加速。全身特立帕肽治疗还加速了这些小鼠的骨折愈合，与对照组相比，PTH治疗的骨折痂中Osx表达增加。总体而言，这些数据提示了特立帕肽介导骨折愈合的一种机制，可能是通过诱导MSCs中的Osx实现的。
