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Suffruticosol A elevates osteoblast differentiation targeting BMP2-Smad/1/5/8-RUNX2 in pre-osteoblasts.

ABSTRACT: The Paeonia suffruticosa ANDR. (P. suffruticosa) is commonly used in traditional medicine for various purposes. Suffruticosol A (Suf-A), isolated from P. suffruticosa, is a beneficial compound with antibiofilm, antivirulence, and anti-inflammatory properties. The aim of the present study was to investigate the biological effects of Suf-A on osteogenic processes in pre-osteoblasts. It was determined here in that Suf-A (>98.02%), isolated from P. suffruticosa, showed no cytotoxicity at 0.1-30 μM; however, it induced cytotoxicity at 50-100 μM in pre-osteoblasts. Suf-A increased osteogenic alkaline phosphatase activity and expression levels of noncollagenous proteins. Adhesion and trans-migration on the extracellular matrix were potentiated by Suf-A, but not by wound-healing migration. Suf-A did not affect autophagy or necroptosis during osteoblast differentiation. We found that Suf-A increased runt-related transcription factor 2 (RUNX2) levels and mineralized matrix formation. RUNX2 expression was mediated by Suf-A-induced BMP2-Smad1/5/8 and mitogen-activated protein kinase signaling, as demonstrated by Noggin, a BMP2 inhibitor. These results suggest that Suf-A is a potential natural osteogenic compound.

SUBMITTER: Yun HM

PROVIDER: S-EPMC10947220 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Suffruticosol A elevates osteoblast differentiation targeting BMP2-Smad/1/5/8-RUNX2 in pre-osteoblasts.

Yun Hyung-Mun HM Kim Bomi B Jeong Yun Hee YH Hong Jin Tae JT Park Kyung-Ran KR

BioFactors (Oxford, England) 20220719 1

The Paeonia suffruticosa ANDR. (P. suffruticosa) is commonly used in traditional medicine for various purposes. Suffruticosol A (Suf-A), isolated from P. suffruticosa, is a beneficial compound with antibiofilm, antivirulence, and anti-inflammatory properties. The aim of the present study was to investigate the biological effects of Suf-A on osteogenic processes in pre-osteoblasts. It was determined here in that Suf-A (>98.02%), isolated from P. suffruticosa, showed no cytotoxicity at 0.1-30 μM; ...[more]

PMID: 35852295

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Project description:BackgroundWe have previously reported that repeated treatment of human periodontal ligament cells and murine pre-osteoblast MC3T3-E1 cells with transforming growth factor-beta 1 (TGF-β1) inhibited their osteoblastic differentiation because of decreased insulin-like growth factor-1 (IGF-1) secretion. We also found that IGF-1/PI3K signaling plays an important role in osteoblast differentiation induced by TGF-β1 treatment; however, the downstream signaling controlling this remains unknown. The aim of this current study is to investigate whether Akt activation is required for osteoblast differentiation.Methodology/principal findingsMC3T3-E1 cells were cultured in osteoblast differentiation medium (OBM) with or without 0.1 ng/mL TGF-β1. OBM containing TGF-β1 was changed every 12 h to provide repeated TGF-β1 administration. MC3T3-E1 cells were infected with retroviral vectors expressing constitutively active (CA) or dominant-negative (DN)-Akt. Alkaline phosphatase (ALP) activity and osteoblastic marker mRNA levels were substantially decreased by repeated TGF-β1 treatment compared with a single TGF-β1 treatment. However, expression of CA-Akt restored ALP activity following TGF-β1 treatment. Surprisingly, ALP activity increased following multiple TGF-β1 treatments as the number of administrations of TGF-β1 increased. Activation of Akt significantly enhanced expression of osteocalcin, but TGF-β1 treatment inhibited this. Mineralization of MC3T3-E1 cells was markedly enhanced by CA-Akt expression under all medium conditions. Exogenous IGF-1 restored the down-regulation of osteoblast-related gene expression by repeated TGF-β1 administration. However, in cells expressing DN-Akt, these levels remained inhibited regardless of IGF-1 treatment. These findings indicate that Akt activation is required for the early phase of osteoblast differentiation of MC3T3-E1 cells induced by TGF-β1. However, Akt activation is insufficient to reverse the inhibitory effects of TGF-β1 in the late stages of osteoblast differentiation.ConclusionsTGF-β1 could be an inducer or an inhibitor of osteoblastic differentiation of MC3T3-E1 cells depending on the state of Akt phosphorylation. Our results indicate that Akt is the molecular switch for TGF-β1-induced osteoblastic differentiation of MC3T3-E1 cells.

Dataset Information

Suffruticosol A elevates osteoblast differentiation targeting BMP2-Smad/1/5/8-RUNX2 in pre-osteoblasts.

Publications

Suffruticosol A elevates osteoblast differentiation targeting BMP2-Smad/1/5/8-RUNX2 in pre-osteoblasts.

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