Diabetes mellitus (DM) affects hundreds of million people worldwide and the impaired bone healing is an important DM-related complication. Understanding how DM affects the activities of osteoclasts and the underlying mechanisms is crucial to the development of effective approaches for accelerating bone healing in DM condition. To date, however, the influence of DM on osteoclasts remains obscure and controversial. In this study, we established a type 2 DM (T2DM) alveolar bone defect model, which closely simulates the pathogenesis of human T2DM, to explore the diabetic osteoclast activity during bone regeneration. We found that a high glucose concentration diminished the formation of osteoclasts, and the differentiation and function of osteoclasts from T2DM rats were suppressed. The degradation of matrix by osteoclasts was significantly reduced at a high glucose concentration. In vivo experiments further indicated that T2DM inhibited osteoclastogenesis and osteoclast activity, and delayed the degradation of matrix during the alveolar bone regeneration in T2DM rats. Our work clarifies the influence of T2DM on osteoclasts, and provides valuable insights for the design of novel scaffolding materials that target on osteoclasts for T2DM bone regeneration. STATEMENT OF SIGNIFICANCE: Impaired bone healing is one of the diabetes mellitus (DM)-related complications. Understanding how DM affects osteoclast activity and scaffolding matrix degradation is pivotal to the development of effective approaches for accelerating bone healing in DM condition. Currently, the influences of DM on osteoclast activity and matrix degradation in bone defect areas, however, remain controversial and obscure. Herein, we established a type 2 DM (T2DM) alveolar bone defect model and our results show that T2DM inhibited osteoclastogenesis and osteoclast activity, and delayed the degradation of scaffolding matrix. Our work clarifies the influence of T2DM on osteoclasts and matrix degradation, and provides insights for the design of novel scaffolding materials that target on osteoclasts for T2DM bone regeneration.

中文翻译：

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2型糖尿病下骨再生中的破骨细胞。

糖尿病（DM）影响全球数亿人，而骨愈合不良是与DM相关的重要并发症。了解DM如何影响破骨细胞的活性及其潜在机制对于开发在DM条件下促进骨愈合的有效方法至关重要。然而，迄今为止，DM对破骨细胞的影响仍然是模糊的和有争议的。在这项研究中，我们建立了一个2型DM（T2DM）牙槽骨缺损模型，该模型紧密模拟了人类T2DM的发病机理，以探讨在骨再生过程中糖尿病破骨细胞的活性。我们发现高浓度的葡萄糖减少了破骨细胞的形成，并抑制了T2DM大鼠的破骨细胞的分化和功能。在高葡萄糖浓度下，破骨细胞对基质的降解作用明显降低。体内实验进一步表明，T2DM抑制了T2DM大鼠肺泡骨再生过程中的破骨细胞生成和破骨细胞活性，并延迟了基质的降解。我们的工作阐明了T2DM对破骨细胞的影响，并为针对破骨细胞的新型支架材料的设计提供了有价值的见解，以实现T2DM骨再生。意义声明：骨愈合不良是与糖尿病（DM）相关的并发症之一。了解DM如何影响破骨细胞活性和脚手架基质降解对于开发在DM条件下加速骨骼愈合的有效方法至关重要。目前，DM对骨缺损区域破骨细胞活性和基质降解的影响仍然存在争议和模糊。在这里，我们建立了一个2型糖尿病（T2DM）牙槽骨缺损模型，我们的研究结果表明T2DM抑制破骨细胞生成和破骨细胞活性，并延迟了脚手架基质的降解。我们的工作阐明了T2DM对破骨细胞和基质降解的影响，并为针对破骨细胞的新型脚手架材料的设计提供了见识，以用于T2DM骨再生。