Bone fracture repair has gained a lot of attention due to the high incidence of delayed union or even nonunion especially in osteoporotic patients, resulting in a dreadful impact on the quality of life. However, current therapies involve the costly expense and hence become unaffordable strategies for fracture recovery. Herein, developing new strategies for better bone repair is essential and urgent. Catalpol treatment has been reported to attenuate bone loss and promote bone formation. However, the mechanisms underlying its effects remain unraveled. Rat bone marrow mesenchymal stem cells (BMSCs) were isolated from rat femurs. BMSC osteogenic ability was assessed using ALP and ARS staining, immunofluorescence, and western blot analysis. BMSC-mediated angiogenic potentials were determined using the western blot analysis, ELISA testing, scratch wound assay, transwell migration assay, and tube formation assay. To investigate the molecular mechanism, the lentivirus transfection was used. Ovariectomized and sham-operated rats with calvaria defect were analyzed using micro-CT, H&E staining, Masson’s trichrome staining, microfil perfusion, sequential fluorescent labeling, and immunohistochemistry assessment after administrated with/without catalpol. Our results manifested that catalpol enhanced BMSC osteoblastic differentiation and promoted BMSC-mediated angiogenesis in vitro. More importantly, this was conducted via the JAK2/STAT3 pathway, as knockdown of STAT3 partially abolished beneficial effects in BMSCs. Besides, catalpol administration facilitated bone regeneration as well as vessel formation in an OVX-induced osteoporosis calvarial defect rat model. The data above showed that catalpol could promote osteogenic ability of BMSC and BMSC-dependent angiogenesis through activation of the JAK2/STAT3 axis, suggesting it may be an ideal therapeutic agent for clinical medication of osteoporotic bone fracture.

中文翻译：

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Catalpol激活STAT3促进成骨-血管生成偶联，从而加速骨质疏松性骨的修复

由于延迟愈合甚至骨不连的发生率很高，尤其是在骨质疏松症患者中，骨骨折修复得到了广泛的关注，从而对生活质量产生了可怕的影响。然而，目前的疗法涉及昂贵的费用，因此成为骨折恢复无法承受的策略。在此，开发更好的骨修复新策略至关重要且紧迫。据报道，Catalpol治疗可减轻骨质流失并促进骨形成。但是，影响其作用的机制仍未阐明。从大鼠股骨中分离出大鼠骨髓间充质干细胞（BMSC）。使用ALP和ARS染色，免疫荧光和蛋白质印迹分析评估BMSC的成骨能力。使用蛋白质印迹分析，ELISA测试确定BMSC介导的血管生成电位，刮擦伤口测定，穿孔迁移测定和管形成测定。为了研究分子机制，使用了慢病毒转染。在使用Catalpol或不使用Catalpol的情况下，使用micro-CT，H＆E染色，Masson三色染色，microfil灌注，顺序荧光标记和免疫组化评估分析了卵巢切除和假手术的颅骨缺损大鼠。我们的结果表明，梓醇在体外增强了BMSC成骨细胞的分化并促进了BMSC介导的血管生成。更重要的是，这是通过JAK2 / STAT3途径进行的，因为STAT3的敲低部分消除了BMSC的有益作用。此外，在OVX诱发的骨质疏松性颅骨缺损大鼠模型中，使用catalpol有助于骨骼再生以及血管形成。