BMP9 and COX-2 form an important regulatory loop in BMP9-induced osteogenic differentiation of mesenchymal stem cells

Wang, Jinhua; Liu, Yingzi; Liang, Yin; Chen, Liang; Huang, Jun; Liu, Yang; Zhang, Ranxi; Zhou, Long-Yang; Yang, Qing; Luo, Jinyong; Zuo, Guo‐Wei; Deng, Zhong‐Liang; He, Bai‐Cheng

doi:10.1016/j.bone.2013.08.015

Cited by 59 publications

(88 citation statements)

References 52 publications

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“…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%

“…Yang et al suggested that OS cells might be maintained in an undifferentiated state secondary to impaired TGF-β/BMP signalling (13). BMP9, a member of BMPs, is known as the most potent osteogenic factor compared to the other family members in mesenchymal stem cells (MSCs) (17,18). However, Luo et al reported that BMPs (including BMP9) were unable to induce bone formation in twelve OS cell lines (including 143B cells) and promoted OS cell growth by locking the cells in the early proliferative phase of the osteogenic pathway (10).…”

Section: Introductionmentioning

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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Section: Discussioncontrasting

confidence: 45%

Section: Introductionmentioning

confidence: 99%

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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“…In order to precisely observe the effects of HIF-1α on the BMP2-induced progression of chondrogenesis and endochondral ossification, a fetal limb culture was performed. Fetal limb cultures can mimic the progression of chondrogenesis and endochondral ossification in vitro [38,51,52]. The results revealed that HIF-1α and BMP2 acted synergistically inin expanding the proliferating chondrocyte zone and inhibiting the BMP2-induced chondrocyte hypertrophy and endochondral ossification zone.…”

Section: Disscussionmentioning

confidence: 99%

HIF-1α as a Regulator of BMP2-Induced Chondrogenic Differentiation, Osteogenic Differentiation, and Endochondral Ossification in Stem Cells

Zhou

Liao

et al. 2015

Cell Physiol Biochem

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Background/Aims: Joint cartilage defects are difficult to treat due to the limited self-repair capacities of cartilage. Cartilage tissue engineering based on stem cells and gene enhancement is a potential alternative for cartilage repair. Bone morphogenetic protein 2 (BMP2) has been shown to induce chondrogenic differentiation in mesenchymal stem cells (MSCs); however, maintaining the phenotypes of MSCs during cartilage repair since differentiation occurs along the endochondral ossification pathway. In this study, hypoxia inducible factor, or (HIF)-1α, was determined to be a regulator of BMP2-induced chondrogenic differentiation, osteogenic differentiation, and endochondral bone formation. Methods: BMP2 was used to induce chondrogenic and osteogenic differentiation in stem cells and fetal limb development. After HIF-1α was added to the inducing system, any changes in the differentiation markers were assessed. Results: HIF-1α was found to potentiate BMP2-induced Sox9 and the expression of chondrogenesis by downstream markers, and inhibit Runx2 and the expression of osteogenesis by downstream markers in vitro. In subcutaneous stem cell implantation studies, HIF-1α was shown to potentiate BMP2-induced cartilage formation and inhibit endochondral ossification during ectopic bone/cartilage formation. In the fetal limb culture, HIF-1α and BMP2 synergistically promoted the expansion of the proliferating chondrocyte zone and inhibited chondrocyte hypertrophy and endochondral ossification. Conclusion: The results of this study indicated that, when combined with BMP2, HIF-1α induced MSC differentiation could become a new method of maintaining cartilage phenotypes during cartilage tissue engineering.

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“…Bone morphogenetic protein 9 (BMP9) has been reported as one of the most potent BMPs to induce osteogenic differentiation in MPCs [9,10], and can be used for bone tissue engineering when combine with some special biomaterials. Although a few essential down-stream targets of BMP9 has been identified, such as Creld2 [11], Hey1 [12], and COX-2 [13], the detail mechanism for BMP9 to induce osteogenic differentiation in MPCs remains unclear yet.…”

Section: Introductionmentioning

confidence: 98%

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

et al. 2014

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BMP9 and COX-2 form an important regulatory loop in BMP9-induced osteogenic differentiation of mesenchymal stem cells

Cited by 59 publications

References 52 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

HIF-1α as a Regulator of BMP2-Induced Chondrogenic Differentiation, Osteogenic Differentiation, and Endochondral Ossification in Stem Cells

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

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