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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.

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Background and objective The Sharpey's fibers of periodontal ligament (PDL) anchor the PDL to alveolar bone and cementum and are essential for the function of PDL. While qualitative analyses of the Sharpey's fibers have been widely explored, a comprehensive quantitative characterization of the Sharpey's fibers is not available. In this work, we selected rat molars as a model and comprehensively characterized the PDL Sharpey's fibers (diameter, density, length, embedding angle, and insertion angle). Materials and methods A total of 24 rat mandibular molars, eight maxillary first molars, and their surrounding alveolar bone were harvested, fixed, rendered anorganic and observed under scanning electron microscopy (SEM). The mandibles and maxillae (n = 4) were harvested, processed, sectioned, and stained with Sirius red for histological observation. SEM images were used for quantitative analyses of diameters and densities of the Sharpey's fibers, while Sirius red staining images were used to measure lengths and angles. The Sharpey's fibers were comprehensively characterized in terms of positions (cervical, middle, and apical thirds), PDL fiber groups (alveolar crest, horizontal, oblique, apical, and interradicular groups), sides (cementum and bone sides), and teeth (mandibular first, second, third molars, and maxillary first molar). Results Our results showed that the characteristic parameters of the Sharpey's fibers varied in different positions, fiber groups, sides, and teeth. Specifically, the median diameter of the Sharpey's fibers on the bone side was significantly greater than that on the cementum side, while the median density of the Sharpey's fibers on the bone side was significantly lower than that on the cementum side, regardless of the positions and teeth. For the same tooth, the median length of the embedded Sharpey's fibers on the bone side was more than two times greater than that on the cementum side. Among all fiber groups, the alveolar crest group had the maximum length of the Sharpey's fibers on the bone side and the minimal length of the Sharpey's fibers on the cementum side. There is an approximate 5‐15° difference between the embedding angle and the insertion angle in each group. The oblique group had the smallest embedding angles on both the bone and cementum sides. Conclusion This study provides a comprehensive and quantitative characterization of the Sharpey's fibers using rat molars as a model. Overall, these parameters varied according to different vertical positions, fiber groups, teeth, and jawbones. The quantitative information of the Sharpey's fibers presented in this work facilitates our understanding of PDL functions and advances the development of biomimetic materials for periodontal tissue regeneration.