BACKGROUND Indian hedgehog (Ihh) signaling pathway is known to play key roles in various aspects of normal endochondral bone development. This study tested the potential roles of high Ihh signaling in the context of injury-induced bone regeneration. METHODS A rabbit tibia defect model was established to test the effects of the implant of Ihh/mesenchymal stem cells (MSCs)/scaffold complex. Computed tomography (CT), gross observation, and standard histological and immunohistological techniques were used to evaluate the effectiveness of the treatment. In vitro studies with MSCs and C3H10T1/2 cells were also employed to further understand the cellular and molecular mechanisms. RESULTS We found that the implanted Ihh/MSCs/scaffold complex promoted bone repair. Consistently, in vitro study found that Ihh induced the upregulation of chondrocytic, osteogenic, and vascular cell markers, both in C3H10T1/2 cells and MSCs. CONCLUSIONS Our study has demonstrated that high Ihh signaling in a complex with MSCs enhanced bone regeneration effectively in a clinically relevant acute injury model. Even though the exact underlying mechanisms are still far from clear, our primary data suggested that enhanced chondrogenesis, osteogenesis, and angiogenesis of MSCs at least partially contribute to the process. This study not only has implications for basic research of MSCs and Ihh signaling pathway but also points to the possibility of direct application of this specific paradigm to clinical bone repair.

中文翻译：

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过度表达 Ihh 的间充质干细胞促进骨修复。

背景 已知印度刺猬 (Ihh) 信号通路在正常软骨内骨发育的各个方面发挥关键作用。该研究测试了高 Ihh 信号在损伤诱导的骨再生背景下的潜在作用。方法建立兔胫骨缺损模型，测试Ihh/间充质干细胞（MSCs）/支架复合物植入的效果。计算机断层扫描 (CT)、大体观察和标准组织学和免疫组织学技术用于评估治疗的有效性。MSCs 和 C3H10T1/2 细胞的体外研究也被用来进一步了解细胞和分子机制。结果我们发现植入的Ihh/MSCs/支架复合物促进了骨修复。一致地，体外研究发现 Ihh 诱导软骨细胞的上调，C3H10T1/2 细胞和 MSC 中的成骨和血管细胞标志物。结论 我们的研究表明，MSCs 复合物中的高 Ihh 信号可有效增强临床相关急性损伤模型中的骨再生。尽管确切的潜在机制仍远未明确，但我们的主要数据表明，MSCs 增强的软骨形成、成骨和血管生成至少部分促成了这一过程。这项研究不仅对 MSCs 和 Ihh 信号通路的基础研究具有重要意义，而且还指出了将该特定范式直接应用于临床骨修复的可能性。结论 我们的研究表明，MSCs 复合物中的高 Ihh 信号可有效增强临床相关急性损伤模型中的骨再生。尽管确切的潜在机制仍远未明确，但我们的主要数据表明，MSCs 增强的软骨形成、成骨和血管生成至少部分促成了这一过程。这项研究不仅对 MSCs 和 Ihh 信号通路的基础研究具有重要意义，而且还指出了将该特定范式直接应用于临床骨修复的可能性。结论 我们的研究表明，MSCs 复合物中的高 Ihh 信号可有效增强临床相关急性损伤模型中的骨再生。尽管确切的潜在机制仍远未明确，但我们的主要数据表明，MSCs 增强的软骨形成、成骨和血管生成至少部分促成了这一过程。这项研究不仅对 MSCs 和 Ihh 信号通路的基础研究具有重要意义，而且还指出了将该特定范式直接应用于临床骨修复的可能性。