The role of COX-2 in mediating the effect of PTEN on BMP9 induced osteogenic differentiation in mouse embryonic fibroblasts

Huang, Jun; Yuan, Shiyun; Wang, Dongxu; Wu, Qiulian; Wang, Xing; Pi, Chang-Jun; Zou, Xiang; Chen, Liang; Ying, Liang-Jun; Wu, Ke; Yang, Junqing; Sun, Wei; Deng, Zhong‐Liang; He, Bai‐Cheng

doi:10.1016/j.biomaterials.2014.08.016

Cited by 38 publications

(60 citation statements)

References 46 publications

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“…2A and B). Similar results were obtained in the analysis of ALP activity, an early maker of osteogenesis (38) (Fig. 2C).…”

Section: Bmp9 Failed To Induce Osteogenic Differentiation Of Os Cellssupporting

confidence: 71%

“…BMP9 signals through the canonical BMP/Smad pathway. BMP9 binds to type II or type I BMP receptors (BMPRII or BMPRI), phosphorylates Smad1/5/8 and forms a complex with Smad4, followed by translocation to the nucleus and regulation of downstream targets (18,38). However, this study suggested that ATRA alone or ATRA combined with BMP9 groups failed to activate the Smad1/5/8 signalling (Fig.…”

Section: Discussioncontrasting

confidence: 45%

“…5A). BMP9 can exert its function through the non-canonical BMP/Smad pathway, involving p38 MAPK and PI3K/Akt (38,49). Thus, we surmised that p38 MAPK might play an important role in this phenomenon.…”

Section: Discussionmentioning

confidence: 99%

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All-trans retinoic acid restored the osteogenic ability of BMP9 in osteosarcoma through the p38 MAPK pathway

Meng

et al. 2017

International Journal of Oncology

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Abstract. Osteosarcoma (OS) is the most common malignant bone tumour and is considered to be a disease caused by a dysfunction in differentiation. Bone morphogenetic protein 9 (BMP9) is the most potent osteogenic factor in mesenchymal stem cells, but it cannot induce osteogenic differentiation in OS cells; this might be one of the determinants in the pathogenesis of OS. All-trans retinoic acid (ATRA) can induce osteogenic differentiation of OS cells and potentiate BMP9-induced osteogenesis in preadipocytes. However, the concomitant effect of ATRA and BMP9 in OS cells is unclear; therefore, in the present study, we focused on this topic. The results showed that BMP9 significantly promoted the proliferation of human OS 143B cells and did not induce osteogenic differentiation of cells in vitro (p<0.01). ATRA inhibited proliferation and induced osteogenesis in 143B cells; these effects could be enhanced by BMP9 overexpression (p<0.05). ATRA could significantly increase the level of phosphorylated p38 MAPK (p-p38) in 143B cells, while BMP9 did not have any significant effect. Notably, BMP9 overexpression enhanced the ability of ATRA to increase the levels of p-p38. Both the osteogenic differentiation and the anti-proliferative activity of BMP9 in the presence of ATRA decreased upon treatment with a specific inhibitor of p38 MAPK (SB203580) (p<0.01). This study indicates that the osteogenic differentiation ability of BMP9 in 143B cells can be restored by ATRA, and the combination of BMP9 and ATRA generated a stronger anti-proliferative effect on 143B cells than ATRA alone. This result may be due to the activation of the p38 MAPK pathway.

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“…2A and B). Similar results were obtained in the analysis of ALP activity, an early maker of osteogenesis (38) (Fig. 2C).…”

Section: Bmp9 Failed To Induce Osteogenic Differentiation Of Os Cellssupporting

confidence: 71%

Section: Discussioncontrasting

confidence: 45%

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All-trans retinoic acid restored the osteogenic ability of BMP9 in osteosarcoma through the p38 MAPK pathway

Meng

et al. 2017

International Journal of Oncology

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“…MEFs were isolated from NIH mice (n=5, obtained from The Animal Center of Chongqing Medical University; Chongqing, China) at post-coitus day 12.5, as previously described (21,22). Each embryo, voided of its internal organs, was dissected and digested with 1 ml of 0.25% trypsin at 37°C for 15 min.…”

Section: Methodsmentioning

confidence: 99%

“…ALP activity was determined using a modified Great Escape SEAP Chemiluminescence assay (BD Biosciences Clontech, San Jose, CA, USA) and/or histochemical staining as previously described (14,21,22). The cells (MEFs) were treated with ATRA, RSG, ATRA and RSG, or the same volume of DMSO as solvent control for 5 and 7 days, and the concentration of ATRA and RSG is 0.4 µ M and 20 µ M, respectively.…”

Section: Methodsmentioning

confidence: 99%

All-trans retinoic acid shifts rosiglitazone-induced adipogenic differentiation to osteogenic differentiation in mouse embryonic fibroblasts

Shao

Chen

Zeng

et al. 2016

International Journal of Molecular Medicine

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Rosiglitazone (RSG) is a potent drug used in the treatment of insulin resistance; however, it is associated with marked skeletal toxicity. RSG-induced osteoporosis may contribute to the promotion of adipogenic differentiation at the expense of osteogenic differentiation in bone marrow stromal cells. The aim of this study was to investigate whether RSG-induced bone toxicity can be reversed by combined treatment with all-trans retinoic acid (ATRA). We examined different osteogenic markers in mouse embryonic fibroblasts (MEFs) following treatment with RSG, ATRA, or RSG and ATRA in combination. We examined the effects of RSG and/or ATRA on ectopic bone formation, and dissected the possible molecular mechanisms underlying this process. We found that ATRA or RSG both induced alkaline phosphatase (ALP) activity in the MEFs, and that the ATRA-induced ALP activity was enhanced by RSG and vice versa. However, only the combination of RSG and ATRA increased the expression of osteopontin and osteocalcin, promoted matrix mineralization, and induced ectopic ossification in MEFs. Mechanistically, we found that the osteogenic differentiation induced by the combination of RSG and ATRA may be mediated partly by suppressing RSG-induced adipogenic differentiation and activating bone morphogenetic protein (BMP)/Smad signaling. On the whole, our findings demonstrate that RSG in combination with ATRA promotes the commitment of MEFs to the osteoblast lineage. Thus, the combination of these two agents may prove to be a promising and novel therapeutic regimen for insulin resistance without skeletal toxicity. It may also be a better strategy with which to prevent RSG-induced osteoporosis.

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Nanosilicate‐Reinforced Silk Fibroin Hydrogel for Endogenous Regeneration of Both Cartilage and Subchondral Bone

Sheng

Chen

Wang

et al. 2022

Adv Healthcare Materials

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Osteochondral defects are characterized by injuries to both cartilage and subchondral bone, which is a result of trauma, inflammation, or inappropriate loading. Due to the unique biological properties of subchondral bone and cartilage, developing a tissue engineering scaffold that can promote dual-lineage regeneration of cartilage and bone simultaneously remains a great challenge. In this study, a microporous nanosilicate-reinforced enzymatically crosslinked silk fibroin (SF) hydrogel is fabricated by introducing montmorillonite (MMT) nanoparticles via intercalation chemistry. In vitro studies show that SF-MMT nanocomposite hydrogel has improved mechanical properties and hydrophilicity, as well as the bioactivities to promote the osteogenic differentiation of bone marrow mesenchymal stem cells and maintain chondrocyte phenotype compared with SF hydrogel. Global proteomic analysis verifies the dual-lineage bioactivities of SF-MMT nanocomposite hydrogel, which are probably regulated by multiple signaling pathways. Furthermore, it is observed that the biophysical interaction of cells and SF-MMT nanocomposite hydrogel is partially mediated by clathrin-mediated endocytosis and its downstream processes. In vivo, the SF-MMT nanocomposite hydrogel effectively promotes osteochondral regeneration as evidenced by macroscopic, micro-CT, and histological evaluation. In conclusion, a functionalized SF-MMT nanocomposite hydrogel is developed with dual-lineage bioactivity for osteochondral regeneration, indicating its potential in osteochondral tissue engineering.

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The role of COX-2 in mediating the effect of PTEN on BMP9 induced osteogenic differentiation in mouse embryonic fibroblasts

Cited by 38 publications

References 46 publications

All-trans retinoic acid restored the osteogenic ability of BMP9 in osteosarcoma through the p38 MAPK pathway

All-trans retinoic acid restored the osteogenic ability of BMP9 in osteosarcoma through the p38 MAPK pathway

All-trans retinoic acid shifts rosiglitazone-induced adipogenic differentiation to osteogenic differentiation in mouse embryonic fibroblasts

Nanosilicate‐Reinforced Silk Fibroin Hydrogel for Endogenous Regeneration of Both Cartilage and Subchondral Bone

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