Peroxisome proliferator-activated receptor-γ and its related pathway in bone marrow mesenchymal stem cell differentiation co-cultured with mechanically stretched ligament fibroblasts

Abstract

The occurrence of pelvic floor dysfunctional disease (PFD) is closely related with elasticity, toughness, and functional changes of the connective tissue of the pelvic support tissue. Bone marrow mesenchymal stem cells (BMSCs) have been confirmed to have the capacity to differentiate into a variety of cell types such as osteoblasts, chondroblasts, adipocytes and fibroblasts. Therefore, BMSCs have the potential to improve the clinical outcomes for PFD. Peroxisome proliferator-activated receptor-γ (PPAR-γ), a ligand activated transcription factor, has acquired a great deal of attention as it is involved in the fibrosis and cell differentiation. However, how it is regulated during the process of the differentiation of BMSCs into fibroblasts remains to be defined. The present study investigated the underlying mechanisms of PPAR-γ effect of mechanical stretch on the differentiation of BMSCs induced by pelvic ligament fibroblasts. PPAR-γ expression was decreased during the differentiation of BMSCs into fibroblasts by co-cultured stretched fibroblasts. Addition of transforming growth factor-β1 (TGF-β1) reduced PPAR-γ expression and promoted the differentiation of BMSCs. With the employment of endogenous ligand, activation of PPAR-γ suppressed the BMSC differentiation. Similar effects were also observed with overexpression of PPAR-γ gene. In addition, decrease of PPAR-γ by the use of shRNA targeting rat PPAR-γ significantly contributed to BMSC differentiation to fibroblasts. These results indicate that PPAR-γ negatively regulates the differentiation of BMSCs into fibroblasts.

Cannabinoid type‐2 receptor agonist, inverse agonist, and anandamide regulation of inflammatory responses in IL‐1β stimulated primary human periodontal ligament fibroblasts

“…It also demonstrated a full agonist activity at GPR18 when screened in its ability to activate p‐ERK (EC 50 3.83 µM) 88 . Additionally, AEA also activates the vanilloid (TRPV1) receptor (potency of 0.7‐5 µM) 89 to regulate bone metabolism in PD, 90 peroxisome proliferator‐activated receptor‐γ (PPAR) (8 µM), 91,92 which are reported to be expressed in PDL cells 93‐95 . Moreover, AEA directly inhibits voltage‐dependent T‐ Type calcium channels (1 µM), 96 which are involved in the proliferation of hPDLFs via bFGF, 97 and the acid‐sensitive K + channel (TASK‐1) at 3 µM, 98 also expressed in hPDLFs 99 .…”

Loss of Lgr4 inhibits differentiation, migration and apoptosis, and promotes proliferation in bone mesenchymal stem cells

“…Mesenchymal stem cells (MSCs) have already been tested in clinical trials, including the treatment of human myocardial infarction, osteogenesis imperfecta, osteoarthritis, and tissue repair (Wei et al, 2013). Although it is currently believed that the therapeutic benefits of BMSCs are due to more complicated mechanisms, it is widely accepted that the BMSC abilities of selfrenewal, multilineage differentiation, and migration were closely related to the efficacy of stem cell therapy (Duchamp de Lageneste et al, 2018;Omoto et al, 2009;Richardson & Hoyland, 2008;Shi et al, 2017;Wei et al, 2013;Zhao et al, 2018).…”

Extracellular vesicles derived from T-cell acute lymphoblastic leukemia inhibit osteogenic differentiation of bone marrow mesenchymal stem cells <i>via</i> miR-34a-5p

“…The levels of osteogenic and adipogenic markers in BMSCs are negatively correlated [40]. PPARγ is an adipogenic marker that has been shown to negatively regulate the differentiation of BMSCs into fibroblasts [41]. FABP4 is a carrier protein for fatty acids that has been identified as a marker associated with adipogenesis in BMSCs [42].…”