Expansion of Bone Precursors through Jun as a Novel Treatment for Osteoporosis-Associated Fractures
Expansion of Bone Precursors through Jun as a Novel Treatment for Osteoporosis-Associated Fractures
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DOI：
10.1016/j.stemcr.2020.02.009
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发表时间：
2020-04-14
影响因子：
5.9
通讯作者：
Wernig, Gerlinde
中科院分区：
文献类型：
--
作者：
Lerbs, Tristan;Cui, Lu;Wernig, Gerlinde
骨质疏松症和骨质疏松性骨折导致生活质量下降和医疗费用高昂。目前的治疗方法可以在一定程度上防止骨质流失和骨折，但有副作用。因此，需要更好的治疗方法。本研究调查了转录因子 Jun 是否具有特定的促成骨功效，以及调节 Jun 是否可以作为骨质疏松相关骨折的新型治疗方法。我们证明异位移植的全骨和不同的骨祖细胞可以增加骨形成。围产期 Jun 诱导会扰乱生长板结构，导致骨骼缩短和增厚的显着表型。从分子角度来看，Jun 可以在骨骼干细胞中诱导刺猬信号传导。在治疗上，Jun 可以加速钻孔缺陷模型中的骨骼生长和愈合。总而言之，这些结果表明，Jun 通过扩大骨祖细胞群并迫使它们进入骨命运来驱动骨形成，为未来的临床应用提供了理论依据。
Osteoporosis and osteoporotic fractures lead to decreased life quality and high healthcare costs. Current treatments prevent losses in bone mass and fractures to some extent but have side effects. Therefore, better therapies are needed. This study investigated whether the transcription factor Jun has a specific pro-osteogenic potency and whether modulating Jun could serve as a novel treatment for osteoporosis-associated fractures. We demonstrate that ectopically transplanted whole bones and distinct osteoprogenitors increase bone formation. Perinatal Jun induction disturbs growth plate architecture, causing a striking phenotype with shortened and thickened bones. Molecularly, Jun induces hedgehog signaling in skeletal stem cells. Therapeutically, Jun accelerates bone growth and healing in a drilling-defect model. Altogether, these results demonstrate that Jun drives bone formation by expanding osteoprogenitor populations and forcing them into the bone fate, providing a rationale for future clinical applications.