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Leonurus sibiricus L. ethanol extract promotes osteoblast differentiation and inhibits osteoclast formation.

ABSTRACT: Leonurus sibiricus L. (LS) is a medicinal plant used in East Asia, Europe and the USA. LS is primarily used in the treatment of gynecological diseases, and recent studies have demonstrated that it exerts anti?inflammatory and antioxidant effects. To the best of our knowledge, the present study demonstrated for the first time that LS may promote osteoblast differentiation and suppress osteoclast differentiation in vitro, and that it inhibited lipopolysaccharide (LPS)?induced bone loss in a mouse model. LS was observed to promote the osteoblast differentiation of MC3T3?E1 cells and upregulate the expression of runt-related transcription factor 2 (RUNX2), a key gene involved in osteoblast differentiation. This resulted in the induction of the expression of various osteogenic genes, including alkaline phosphatase (ALP), osteonectin (OSN), osteopontin (OPN), type I collagen (COL1) and bone sialoprotein (BSP). LS was also observed to inhibit osteoclast differentiation and bone resorption. The expression levels of nuclear factor of activated T?cells 1 (NFATc1) and c?Fos were inhibited following LS treatment. NFATc1 and c?Fos are key markers of osteoclast differentiation that inhibit receptor activator of nuclear factor??? ligand (RANKL)?induced mitogen?activated protein kinase (MAPKs) and nuclear factor (NF)??B. As a result, LS suppressed the expression of osteoclast?associated genes, such as matrix metallopeptidase?9 (MMP?9), cathepsin K (Ctsk), tartrate?resistant acid phosphatase (TRAP), osteoclast?associated immunoglobulin?like receptor (OSCAR), c?src, c?myc, osteoclast stimulatory transmembrane protein (OC?STAMP) and ATPase H+ transporting V0 subunit d2 (ATP6v0d2). Consistent with the in vitro results, LS inhibited the reduction in bone mineral density and the bone volume/total volume ratio in a mouse model of LPS?induced osteoporosis. These results suggest that LS may be a valuable agent for the treatment of osteoporosis and additional bone metabolic diseases.

SUBMITTER: Kim JH

PROVIDER: S-EPMC6657961 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Leonurus sibiricus L. ethanol extract promotes osteoblast differentiation and inhibits osteoclast formation.

Kim Jae-Hyun JH Kim Minsun M Jung Hyuk-Sang HS Sohn Youngjoo Y

International journal of molecular medicine 20190708 3

Leonurus sibiricus L. (LS) is a medicinal plant used in East Asia, Europe and the USA. LS is primarily used in the treatment of gynecological diseases, and recent studies have demonstrated that it exerts anti‑inflammatory and antioxidant effects. To the best of our knowledge, the present study demonstrated for the first time that LS may promote osteoblast differentiation and suppress osteoclast differentiation in vitro, and that it inhibited lipopolysaccharide (LPS)‑induced bone loss in a mouse ...[more]

PMID: 31524244

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Project description:The Pacific oyster, Crassostrea gigas, is well-known as a nutritious food. Recently, we revealed that fermented extract of C. gigas (FO) inhibited ovariectomy-induced osteoporosis, resulting from suppression of osteoclastogenesis. However, since the beneficial effect of FO on osteogenesis is poorly understood, it was examined in mouse preosteoblast MC3T3-E1 cells, human osteosarcoma MG-63 osteoblast-like cells, and zebrafish larvae in this study. We found that FO increased mitochondrial activity from days 1 to 7; however, total cell number of MC3T3-E1 cells gradually decreased without any change in cell viability, which suggests that FO stimulates the differentiation of MC3T3-E1 cells. FO also promoted the expression of osteoblast marker genes, including runt-related transcription factor 2 (mRUNX2), alkaline phosphatase (mALP), collagen type I ?1 (mCol1?1), osteocalcin (mOCN), osterix (mOSX), bone morphogenetic protein 2 (mBMP2), and mBMP4 in MC3T3-E1 cells accompanied by a significant increase in ALP activity. FO also increased nuclear translocation of RUNX2 and OSX transcription factors, ALP activity, and calcification in vitro along with the upregulated expression of osteoblast-specific marker proteins such as RUNX2, ALP, Col1?1, OCN, OSX, and BMP4. Additionally, FO enhanced bone mineralization (calcein intensity) in zebrafish larvae at 9 days post-fertilization comparable to that in the ?-glycerophosphate (GP)-treated group. All the tested osteoblast marker genes, including zRUNX2a, zRUNX2b, zALP, zCol1a1, zOCN, zBMP2, and zBMP4, were also remarkably upregulated in the zebrafish larvae in response to FO. It also promoted tail fin regeneration in adult zebrafish as same as the GP-treated groups. Furthermore, not only FO positively regulate ?-catenin expression and Wnt/?-catenin luciferase activity, but pretreatment with a Wnt/?-catenin inhibitor (FH535) also significantly decreased FO-mediated bone mineralization in zebrafish larvae, which indicates that FO-induced osteogenesis depends on the Wnt/?-catenin pathway. Altogether, the current study suggests that the supplemental intake of FO has a beneficial effect on osteogenesis.

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Leonurus sibiricus L. ethanol extract promotes osteoblast differentiation and inhibits osteoclast formation.

Publications

Leonurus sibiricus L. ethanol extract promotes osteoblast differentiation and inhibits osteoclast formation.

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