Recombinant irisin enhances the extracellular matrix formation, remodeling potential, and differentiation of human periodontal ligament cells cultured in 3D

Abstract

Background Irisin is expressed in human periodontal ligament (hPDL), and its administration enhances growth, migration and matrix deposition in hPDL cells cultured in monolayers in vitro. Objectives To identify whether irisin affects the gene expression patterns directing the morphology, mechanical properties, extracellular matrix (ECM) formation, osteogenic activity and angiogenic potential in hPDL cell spheroids cultured in 3D. Materials and Methods Spheroids of primary human hPDL cells were generated in a rotational 3D culture system and treated with or without irisin. The gene expression patterns were evaluated by Affymetrix microarrays. The morphology of the spheroids was characterized using histological staining. Mechanical properties were quantified by nanoindentation. The osteogenic and angiogenic potential of spheroids were assessed through immunofluorescence staining for collagen type I, periostin fibronectin and von Willebrand factor (vWF), and mRNA expression of osteogenic markers. The secretion of multiple myokines was evaluated using Luminex immunoassays. Results Approximately 1000 genes were differentially expressed between control and irisin‐treated groups by Affymetrix. Several genes related to ECM organization were differentially expressed, and multiple deubiquitinating enzymes were upregulated in the irisin‐exposed samples analyzed. These represent cellular and molecular mechanisms indicative of a role for irisin in tissue remodeling. Irisin induced a rim‐like structure on the outer region of the hPDL spheroids, ECM‐related protein expression and the stiffness of the spheroids were enhanced by irisin. The expression of osteogenic and angiogenetic markers was increased by irisin. Conclusions Irisin altered the morphology in primary hPDL cell‐derived spheroids, enhanced its ECM deposition, mechanical properties, differentiation and remodeling potential.

The Role of the Myokine Irisin in the Protection and Carcinogenesis of the Gastrointestinal Tract

“…Existing evidence suggests that recreational physical activity may have a protective effect on periodontal health [60,61]. Indeed, current in vitro studies reveal the involvement of irisin in differentiation, growth, and migration, as well as extracellular matrix formation in various dental cell lines [62][63][64][65][66][67][68][69][70][71][72]. It has been reported that the p38 MAPK and AKT signaling pathways are involved in irisin's effects [62,65,72].…”

Obesity, Metabolic Syndrome, and Osteoarthritis Require Integrative Understanding and Management

“…Recent studies reveal that irisin might play a protective role in joint health, preventing or slowing OA progression. In vitro studies underscore irisin’s role in increasing collagen type II and aggrecan ECM production by chondrocytes [ 150 ] as well as chondrogenic differentiation [ 151 ] with potential positive effects on cartilage maintenance and repair. Irisin was shown to decrease inflammatory cytokines in chondrocytes, including interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α), potentially protecting articular joints [ 152 ].…”