Osteoclasts in bone regeneration under type 2 diabetes mellitus

Abstract

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.

Systemic elucidation on the potential bioactive compounds and hypoglycemic mechanism of Polygonum multiflorum based on network pharmacology

“…Arachidonic acid metabolism: the altered arachidonic acid metabolism and the increased ratio of thromboxane A2 to prostacyclin, which favored an enhanced thrombotic state, may play a role in the accelerated vascular disease of diabetes mellitus [84]. Osteoclast differentiation: it was reported that T2DM could inhibit osteoclastogenesis and osteoclast activity, and delay the degradation of matrix during the alveolar bone regeneration in T2DM rats [85].…”

Heparinized chitosan stabilizes the bioactivity of BMP-2 and potentiates the osteogenic efficacy of demineralized bone matrix

“…Many proteolytic enzymes such as MMP-2, MMP-9, or cathepsin-K were involved in bone remodeling process [32], and MMPs were key degrading enzyme expressed in either physiological [33] or pathological conditions including osteoarthritis [34], and osteoporosis [35]. The concentration of MMP-2 increased around two times, and MMP-9 increased around ten times under bone formation and disease environment [36][37][38]. In this MMP-9 enriched condition, we observed all PBS, MeGC, and Hep-MeGC groups suffered decrement of BMP-2 bioactivity ( Fig.…”

Heparinized Chitosan Stabilizes the Bioactivity of BMP-2 and Potentiates the Osteogenic Efficacy of Demineralized Bone Matrix

“…Many proteolytic enzymes such as MMP-2, MMP-9, or cathepsin-K were involved in bone remodeling process [32], and MMPs were key degrading enzyme expressed in either physiological [33] or pathological conditions including osteoarthritis [34], and osteoporosis [35]. The concentration of MMP-2 increased around two times, and MMP-9 increased around ten times under bone formation and disease environment [36][37][38]. In this MMP-9 enriched condition, we observed all PBS, MeGC, and Hep-MeGC groups suffered decrement of BMP-2 bioactivity (Figure 2a).…”