ABSTRACT
@#Adiponectin, an adipocytokine secreted by adipocytes, has emerged as a potential treatment agent for type 2 diabetes. Adiponectin plays a variety of physiological roles in regulating glucolipid metabolism, oxidative stress, inflammatory responses and bone metabolism by binding to its receptors expressed on a variety of cells and tissues. Numerous studies have confirmed the strong association of adiponectin with type 2 diabetes-related periodontitis. Adiponectin can improve systemic insulin resistance by increasing insulin sensitivity and promoting insulin secretion. It improves the periodontal inflammatory response by inhibiting the expression of proinflammatory cytokines induced by Porphyromonas gingivalis lipopolysaccharide and promoting M2-type polarization of macrophages. In addition, adiponectin inhibits osteoclast differentiation and maturation through various pathways, such as Wnt/β-catenin and NF-κ, and promotes osteoblast differentiation to regulate bone metabolism, thus improving periodontal bone resorption and destruction. Therefore, adiponectin is expected to become a therapeutic target for type 2 diabetes-related periodontitis. Due to the physiological characteristics of adiponectin, its clinical application has been somewhat limited. This article reviews the latest research progress on adiponectin in type 2 diabetes-related periodontitis, aiming to elucidate the possible effects of adiponectin on type 2 diabetes-related periodontitis in terms of glycemic control, anti-inflammation and bone metabolism and to provide some opinions on the treatment of this disease and the development of relevant drugs.
ABSTRACT
BACKGROUND: Spontaneous spheroid culture is a novel three-dimensional (3D) culture strategy for the rapid and efficient selection of progenitor cells. The objectives of this study are to investigate the pluripotency and differentiation capability of spontaneous spheroids from alveolar bone-derived mesenchymal stromal cells (AB-MSCs); compare the advantages of spontaneous spheroids to those of mechanical spheroids; and explore the mechanisms of stemness enhancement during spheroid formation from two-dimensional (2D) cultured cells. METHODS: AB-MSCs were isolated from the alveolar bones of C57BL/6 J mice. Spontaneous spheroids formed in low-adherence specific culture plates. The stemness, proliferation, and multi-differentiation capacities of spheroids and monolayer cultures were investigated by reverse transcription quantitative polymerase chain reaction (RT-qPCR), immunofluorescence, alkaline phosphatase (ALP) activity, and oil-red O staining. The pluripotency difference between the spontaneous and mechanical spheroids was analyzed using RT-qPCR. Hypoxia-inducible factor (HIFs) inhibition experiments were performed to explore the mechanisms of stemness maintenance in AB-MSC spheroids. RESULTS: AB-MSCs successfully formed spontaneous spheroids after 24 h. AB-MSC spheroids were positive for MSC markers and pluripotency markers (Oct4, KLF4, Sox2, and cMyc). Spheroids showed higher Ki67 expression and lower Caspase3 expression at 24 h. Under the corresponding conditions, the spheroids were successfully differentiated into osteogenic and adipogenic lineages. AB-MSC spheroids can induce neural-like cells after neurogenic differentiation. Higher expression of osteogenic markers, adipogenic markers, and neurogenic markers (NF-M, NeuN, and GFAP) was found in spheroids than in the monolayer. Spontaneous spheroids exhibited higher stemness than mechanical spheroids did. HIF-1α and HIF-2α were remarkably upregulated in spheroids. After HIF-1/2α-specific inhibition, spheroid formation was significantly reduced. Moreover, the expression of the pluripotency genes was suppressed. CONCLUSIONS: Spontaneous spheroids from AB-MSCs enhance stemness and pluripotency. HIF-1/2α plays an important role in the stemness regulation of spheroids. AB-MSC spheroids exhibit excellent multi-differentiation capability, which may be a potent therapy for craniomaxillofacial tissue regeneration.