MGP Regulates Perivascular Adipose-Derived Stem Cells Differentiation Toward Smooth Muscle Cells Via BMP2/SMAD Pathway Enhancing Neointimal Formation.

Perivascular adipose-derived stem cells (PV-ADSCs) could differentiate into smooth muscle cells (SMCs), participating in vascular remodeling. However, its underlying mechanism is not well explored. Our previous single-cell RNA-sequencing dataset identified a unique expression of matrix Gla protein (MGP) in PV-ADSCs compared with subcutaneous ADSCs. MGP involves in regulating SMC behaviors in vascular calcification and atherosclerosis. In this study, we investigated MGP's role in PV-ADSCs differentiation toward SMCs in vitro and in vascular remodeling in vivo. PV-ADSCs were isolated from perivascular regions of mouse aortas. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blot, and immunofluorescence confirmed higher MGP expression in PV-ADSCs. The MGP secretion increased along PV-ADSCs differentiation toward SMCs in response to transforming growth factor-beta 1 (TGF-ß1). Lentivirus knockdown of MGP markedly promoted the bone morphogenetic protein 2 (BMP2) expression and phosphorylation of SMAD1/5/8 in PV-ADSCs, subsequently inhibiting its differentiation toward SMCs. Such inhibition could be partially reversed by further application of BMP2 inhibitors. On the contrary, exogenous MGP inhibited BMP2 expression and SMAD1/5/8 phosphorylation in PV-ADSCs, thereby promoting its differentiation toward SMCs. Transplantation of cultured PV-ADSCs, which was pretreated by MGP knockdown, in mouse femoral artery guide-wire injury model significantly alleviated neointimal hyperplasia. In conclusion, MGP promoted the differentiation of PV-ADSCs toward SMCs through BMP2/SMAD-mediated signaling pathway. This study offers a supplement to the society of perivascular tissues and PV-ADSCs.

Spirulina maxima reduces inflammation and alveolar bone loss in Porphyromonas gingivalis-induced periodontitis.

BACKGROUND: Periodontitis is a common oral disease characterized as inflammation on gingival tissue and alveolar bone resorption. Spirulina maxima has been reported to have anti-oxidative and anti-inflammatory effects on gastric ulcers. However, its effects on gingival inflammation and alveolar bone resorption of periodontitis have not been studied. PURPOSE: This study was designed to investigate the effects of S. maxima on the P. gingivalis-induced periodontitis and to elucidate its mechanism. METHODS: The phycocyanin contents in S. maxima were identified by high-performance liquid chromatography. 8-week old SD rats were induced periodontitis by inoculation with P. gingivalis for 14 days. The rats were then orally treated with S. maxima 100, 200, 400 mg/kg, or indomethacin (IND, positive control) 5 mg/kg for an additional 14 days. Inflammatory responses, expressions of collagenases in gingival tissue, osteoclast formation and activation, alveolar bone resorption, osteogenesis-related markers, and BMP2/Smad signaling in alveolar bone were measured. RESULTS: Pro-inflammatory cytokines such as TNF-α, IL-1ß, IL-6, and inflammatory transcription factor NF-κB were decreased in gingival tissue by S. maxima administration. Also, myeloperoxidase (MPO) activity and matrix metalloproteinase (MMPs) expression were decreased by S. maxima administration. Conversely, S. maxima increased IL-4, anti-inflammatory cytokine from Th2 cells. The osteoprotegerin (OPG) / receptor activator of NF-κB ligand (RANKL) expression ratio, which represents osteoclast-osteoblast balance, was increased in S. maxima-treated groups. The alveolar bone loss and the number of TRAP-positive osteoclast cells were also declined in S. maxima-treated groups while the osteoblasts count was increased. Besides, in S. maxima-treated groups, the osteogenesis-related factors were promoted and BMP-2/Smad pathway was up-regulated in a periodontitis condition. CONCLUSION: S. maxima reduces periodontitis induced by P. gingivalis through anti-inflammatory effect and resultant reduction in bone loss, suggesting that S. maxima might be a potential agent for treating periodontitis.