The roles of autophagy in osteogenic differentiation in rat ligamentum fibroblasts: Evidence and possible implications

Yang, Yueping; Lin, Zongming; Cheng, Jiangwei; Ding, Sheng; Mao, Weiwei; Shi, Sheng; Liang, Biru; Jiang, Lei‐Sheng

doi:10.1096/fj.201903216rr

Cited by 13 publications

(8 citation statements)

References 39 publications

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“…Ca2 + deposition was achieved by activating autophagy to remove misfolded proteins to meet the high energy requirements of the mineralization process [ 51 ]. An in vitro study found that the mineralization of osteoblasts could be reduced by knocking out the autophagy-related gene Beclin-1 or by inhibiting the autophagy with autophagy inhibitors [ 52 ]. Similar in vivo study also found that Atg7 deficiency impeded osteoblast mineralization and promoted apoptosis in osteoblast-specific Atg7 condition knockout (cKO) mice, while reconstitution of Atg7 could improve ER stress and restore skeletal balance [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

Glucosamine delays the progression of osteoporosis in senile mice by promoting osteoblast autophagy

Huang

Zheng

et al. 2022

Nutr Metab (Lond)

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Background Senile osteoporosis (SOP) is one of the most prevalent diseases that afflict the elderly population, which characterized by decreased osteogenic ability. Glucosamine (GlcN) is an over-the-counter dietary supplement. Our previous study reported that GlcN promotes osteoblast proliferation by activating autophagy in vitro. The purpose of this study is to determine the effects and mechanisms of GlcN on senile osteoporosis and osteogenic differentiation in vivo. Methods Aging was induced by subcutaneous injection of d-Galactose (d-Gal), and treated with GlcN or vehicle. The anti-senile-osteoporosis effect of GlcN was explored by examining changes in micro-CT, serum indicators, body weight, protein and gene expression of aging and apoptosis. Additionally, the effects of GlcN on protein and gene expression of osteogenesis and autophagy were observed by inhibiting autophagy with 3-methyladenine (3-MA). Results GlcN significantly improved bone mineral density (BMD) and bone micro-architecture, decreased skeletal senescence and apoptosis and increased osteogenesis in d-Gal induced osteoporotic mice. While all effect was reversed with 3-MA. Conclusion GlcN effectively delayed the progression of osteoporosis in senile osteoporotic mice by promoting osteoblast autophagy. This study suggested that GlcN may be a prospective candidate drug for the treatment of SOP.

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Section: Discussionmentioning

confidence: 99%

Glucosamine delays the progression of osteoporosis in senile mice by promoting osteoblast autophagy

Huang

Zheng

et al. 2022

Nutr Metab (Lond)

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“…Ca2 + deposition was achieved by activating autophagy to remove misfolded proteins to meet the high energy requirements of the mineralization process [51]. An in vitro study found that the mineralization of osteoblasts could be reduced by knocking out the autophagy-related gene Beclin-1 or by inhibiting the autophagy with autophagy inhibitors [52]. Similar in vivo study also found that Atg7 de ciency impeded osteoblast mineralization and promoted apoptosis in osteoblast-speci c Atg7 condition knockout (cKO) mice, while reconstitution of Atg7 could improve ER stress and restore skeletal balance [53].…”

Section: Discussionmentioning

confidence: 99%

Glucosamine Delays the Progression of Osteoporosis in Senile Mice by Promoting Osteoblast Autophagy

Huang

Zheng

et al. 2022

Preprint

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Background: Senile osteoporosis (SOP) is one of the most prevalent diseases that afflict the elderly population, which characterized by decreased osteogenic ability. Glucosamine (GlcN) is an over-the-counter dietary supplement. Our previous study reported that GlcN promotes osteoblast proliferation by activating autophagy in vitro. The purpose of this study is to determine the effects and mechanisms of GlcN on senile osteoporosis and osteogenic differentiation in vivo.Methods: Aging was induced by subcutaneous injection of D-Galactose (D-Gal), and treated with GlcN or vehicle. The anti-senile-osteoporosis effect of GlcN was explored by examining changes in micro-CT, serum indicators, body weight, protein and gene expression of aging and apoptosis. Additionally, the effects of GlcN on protein and gene expression of osteogenesis and autophagy were observed by inhibiting autophagy with 3-Methyladenine (3-MA).Results: GlcN significantly improved bone mineral density (BMD) and bone micro-architecture, decreased skeletal senescence and apoptosis and increased osteogenesis in D-Gal induced osteoporotic mice. While all effect was reversed with 3-MA.Conclusion: GlcN effectively delayed the progression of osteoporosis in senile osteoporotic mice by promoting osteoblast autophagy. This study suggested that GlcN may be a prospective candidate drug for the treatment of SOP.

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“…Autophagy, a fundamental process, sequesters intracellular constituents to deliver them to lysosomes that degrade the intracellular components and recycle them into macromolecule precursors (Chang, 2020). Defective autophagy leads to the senescence of mesenchymal stem cells and bone loss (Li et al, 2018;Yang et al, 2020). Thus, autophagy is an indispensable process in osteogenic differentiation.…”

Section: Discussionmentioning

confidence: 99%

CHNQD-00603 Promotes Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells by the miR-452-3p-Mediated Autophagy Pathway

Xin¹,

Li²,

Gao³

et al. 2021

Front. Cell Dev. Biol.

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Background: Periodontitis is a chronic and progressive disease accompanied by bone loss. It is still a challenge to restore the bone structure. The osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) plays a decisive role in bone restoration and regeneration. Marine natural products (MNPs) have multiple biological activities, including anti-tumor and anti-inflammatory properties. However, the exploration of MNPs in osteogenesis is far from sufficient.Methods: We obtained a series of derivatives through structural optimization from 4-phenyl-3,4-dihydroquinolin-2(1H)-one alkaloid isolated from Scopulariopsis sp. Some preliminary cytological experiments showed that CHNQD-00603, obtained by adding a methoxy group to the position C3 and a hydroxyl group to the position C4 of 4-phenyl-3,4-dihydroquinolin-2(1H)-one, might promote the osteogenic differentiation of BMSCs. To further investigate the effects of CHNQD-00603 on BMSCs, we performed a CCK-8 assay and qRT-PCR, alkaline phosphatase staining (ALP), and alizarin red S staining to assess the cytotoxicity and the ability of osteogenic differentiation of CHNQD-00603. The autophagy level was assessed and validated by WB, qRT-PCR, and transmission electron microscopy. Then, 3-methyladenine (3-MA) was added to further examine the role of autophagy. Based on the expression of autophagy-related genes, we predicted and examined the potential miRNAs by bioinformatics.Results: CCK-8 assay showed that CHNQD-00603 at 1 µg/ml did not influence BMSCs activity. However, the proliferation rate decreased from the seventh day. qRT-PCR, ALP staining, ALP activity assay, and Alizarin red S staining showed that the best concentration of CHNQD-00603 to promote osteogenic differentiation was 1 µg/ml. Further investigations indicated that CHNQD-00603 activated autophagy, and the inhibition of autophagy by 3-MA attenuated CHNQD-00603-enhanced osteogenic differentiation. Subsequently, the findings from bioinformatics and qRT-PCR indicated that miR-452-3p might be a regulator of autophagy and osteogenesis. Furthermore, we transfected BMSCs with miR-452-3p NC and mimics separately to further determine the function of miR-452-3p. The data showed that the overexpression of miR-452-3p moderated the level of autophagy and osteogenic differentiation of CHNQD-00603-treated BMSCs.Conclusion: Our data suggested that CHNQD-00603 promoted the osteogenic differentiation of BMSCs by enhancing autophagy. Meanwhile, miR-452-3p played a regulatory role in this process.

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The roles of autophagy in osteogenic differentiation in rat ligamentum fibroblasts: Evidence and possible implications

Cited by 13 publications

References 39 publications

Glucosamine delays the progression of osteoporosis in senile mice by promoting osteoblast autophagy

Glucosamine delays the progression of osteoporosis in senile mice by promoting osteoblast autophagy

Glucosamine Delays the Progression of Osteoporosis in Senile Mice by Promoting Osteoblast Autophagy

CHNQD-00603 Promotes Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells by the miR-452-3p-Mediated Autophagy Pathway

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