Purpose: Clinically, it is challenging to manage diabetic patients with periodontitis. Biochemically, both involve a wide range of inflammatory/collagenolytic conditions which exacerbate each other in a "bi-directional manner." However, standard treatments for this type of periodontitis rely on reducing the bacterial burden and less on controlling hyperinflammation/excessive-collagenolysis. Thus, there is a crucial need for new therapeutic strategies to modulate this excessive host response and to promote enhanced resolution of inflammation. The aim of the current study is to evaluate the impact of a novel chemicallymodified curcumin 2.24 (CMC2.24) on host inflammatory response in diabetic rats. Methods: Type I diabetes was induced by streptozotocin injection; periodontal breakdown then results as a complication of uncontrolled hyperglycemia. Non-diabetic rats served as controls. CMC2.24, or the vehicle-alone, was administered by oral gavage daily for 3 weeks to the diabetics. Micro-CT was used to analyze morphometric changes and quantify bone loss. MMPs were analyzed by gelatin zymography. Cell function was examined by cell migration assay, and cytokines and resolvins were measured by ELISA. Results: In this severe inflammatory disease model, administration of the pleiotropic CMC2.24 was found to normalize the excessive accumulation and impaired chemotactic activity of macrophages in peritoneal exudates, significantly decrease MMP-9 and proinflammatory cytokines to near normal levels, and markedly increase resolvin D 1 (RvD 1 ) levels in the thioglycolate-elicited peritoneal exudates (tPE). Similar effects on MMPs and RvD 1 were observed in the non-elicited resident peritoneal washes (rPW). Regarding clinical relevance, CMC2.24 significantly inhibited the loss of alveolar bone height, volume and mineral density (ie, diabetes-induced periodontitis and osteoporosis).
Conclusion:In conclusion, treating hyperglycemic diabetic rats with CMC2.24 (a triketonic phenylaminocarbonyl curcumin) promotes the resolution of local and systemic inflammation, reduces bone loss, in addition to suppressing collagenolytic MMPs and proinflammatory cytokines, suggesting a novel therapeutic strategy for treating periodontitis complicated by other chronic diseases.
The biological effect of ultrasound on bone regeneration has been well documented, yet the underlying mechanotransduction mechanism is largely unknown. In relation to the mechanobiological modulation of the cytoskeleton and Ca 2+ influx by short-term focused acoustic radiation force (FARF), the current study aimed to visualize and quantify Ca 2+ oscillations in real-time of in situ and in vivo osteocytes in response to focused low-intensity pulsed ultrasound (FLIPUS). For in situ studies, fresh mice calvaria were subjected to FLIPUS stimulation at 0.05, 0.2, 0.3, and 0.7 W. For the in vivo study, 3-month-old C57BL/6J Ai38/Dmp1-Cre mice were subjected to FLIPUS at 0.15, 1, and 1.5 W. As observed via real-time confocal imaging, in situ FLIPUS led to more than 80% of cells exhibiting Ca 2+ oscillations at 0.3-0.7 W and led to a higher number of Ca 2+ spikes with larger values at >0.3 W. In vivo FLIPUS at 1-1.5 W led to more than 90% of cells exhibiting Ca 2+ oscillations. Higher FLIPUS energies led to larger Ca 2+ spike magnitudes. In conclusion, this study provided a pilot study of both in situ and in vivo osteocytic Ca 2+ oscillations under noninvasive FARF, which aids further exploration of the mechanosensing mechanism of the controlled bone cell motility response to the stimulus.
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