All-trans retinoic acid modulates bone morphogenic protein 9-induced osteogenesis and adipogenesis of preadipocytes through BMP/Smad and Wnt/β-catenin signaling pathways

Liu, Yang; Liu, Yingzi; Zhang, Ranxi; Wang, Xing; Fan, Huang; Zhang, Yan; Nie, Min; Huang, Jun; Wang, Yuanzheng; Wang, Yang; Chen, Liang; Liang, Yin; He, Bai‐Cheng; Deng, Zhong‐Liang

doi:10.1016/j.biocel.2013.11.018

Cited by 59 publications

(82 citation statements)

References 47 publications

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“…[105] Upon treatment with both BMP-9 and all-trans retinoic acid however, levels of osteopontin and OCN were significantly greater compared with the BMP-9-treated cells. [105] Bone-specific transcription factors such as Runx2, OSX, distal-less homeobox 5 (Dlx5) and matrix mineralisation were also upregulated as a result of the combined treatment. [105] Interestingly, all-trans retinoic acid has been reported to suppress adipogenesis by BMP-9.…”

Section: Potential Agents Referencementioning

confidence: 99%

“…[105] Bone-specific transcription factors such as Runx2, OSX, distal-less homeobox 5 (Dlx5) and matrix mineralisation were also upregulated as a result of the combined treatment. [105] Interestingly, all-trans retinoic acid has been reported to suppress adipogenesis by BMP-9.…”

Section: Potential Agents Referencementioning

confidence: 99%

“…[106] For instance, BMP-9 markedly upregulated ALP activity in preadipocytes, and this effect was synergistically enhanced after addition of alltrans retinoic acid. [105] Additionally, retinoic acid alone is incapable of inducing late-stage osteoblastogenesis as indicated by its failure to upregulate osteopontin and OCN levels, whereas BMP-9 alone resulted in increased levels of both bone markers. [105] Upon treatment with both BMP-9 and all-trans retinoic acid however, levels of osteopontin and OCN were significantly greater compared with the BMP-9-treated cells.…”

Section: Potential Agents Referencementioning

confidence: 99%

“…[105] Additionally, retinoic acid alone is incapable of inducing late-stage osteoblastogenesis as indicated by its failure to upregulate osteopontin and OCN levels, whereas BMP-9 alone resulted in increased levels of both bone markers. [105] Upon treatment with both BMP-9 and all-trans retinoic acid however, levels of osteopontin and OCN were significantly greater compared with the BMP-9-treated cells. [105] Bone-specific transcription factors such as Runx2, OSX, distal-less homeobox 5 (Dlx5) and matrix mineralisation were also upregulated as a result of the combined treatment.…”

Section: Potential Agents Referencementioning

confidence: 99%

“…[101] BMP-9 is known to mediate both adipocyte and osteoblast differentiation. [105] Due to existing evidence regarding the plasticity between the two lineages, BMP-9 has now been investigated as a potential therapeutic agent for osteoporosis. Among the 14 members of the BMP family, BMP-9 possesses one of the most potent osteoinductive activities alongside BMP-2 and BMP-6.…”

Section: Potential Agents Referencementioning

confidence: 99%

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Transdifferentiation of adipocytes to osteoblasts: potential for orthopaedic treatment

Lin

Dass

2018

Journal of Pharmacy and Pharmacology

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Objectives As both adipocytes and osteoblasts originate from the same pool of mesenchymal stem cells, increasing clinical evidence has emerged of the plasticity between the two lineages. For instance, the downregulation of osteoblast differentiation and upregulation of adipogenesis are common features of conditions such as multiple myeloma, obesity and drug-induced bone loss in diabetes mellitus. However, despite in-vitro and in-vivo observations of adipocyte transdifferentiation into osteoblasts, little is known of the underlying mechanisms. Key findings This review summarises the current knowledge of this particular transdifferentiation process whereby the Wnt/b-catenin signalling pathway and Runx2 overexpression have been postulated to play a critical role. Summary Furthermore, due to the possibility of a novel therapy in the treatment of bone conditions, a number of agents with the potential to induce adipo-toosteoblast transdifferentiation have been investigated such as all-trans retinoic acid, bone morphogenetic protein-9 and vascular endothelial growth factor.

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Section: Potential Agents Referencementioning

confidence: 99%

Section: Potential Agents Referencementioning

confidence: 99%

Section: Potential Agents Referencementioning

confidence: 99%

Section: Potential Agents Referencementioning

confidence: 99%

Section: Potential Agents Referencementioning

confidence: 99%

See 3 more Smart Citations

Transdifferentiation of adipocytes to osteoblasts: potential for orthopaedic treatment

Lin

Dass

2018

Journal of Pharmacy and Pharmacology

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Bone morphogenetic proteins: A powerful osteoinductive compound with non‐negligible side effects and limitations

et al. 2014

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Healing and regeneration of large bone defects leading to non-unions is a great concern in orthopedic surgery. Since auto- and allografts have limitations, bone tissue engineering and regenerative medicine (TERM) has attempted to solve this issue. In TERM, healing promotive factors are necessary to regulate the several important events during healing. An ideal treatment strategy should provide osteoconduction, osteoinduction, osteogenesis, and osteointegration of the graft or biomaterials within the healing bone. Since many materials have osteoconductive properties, only a few biomaterials have osteoinductive properties which are important for osteogenesis and osteointegration. Bone morphogenetic proteins (BMPs) are potent inductors of the osteogenic and angiogenic activities during bone repair. The BMPs can regulate the production and activity of some growth factors which are necessary for the osteogenesis. Since the introduction of BMP, it has added a valuable tool to the surgeon's possibilities and is most commonly used in bone defects. Despite significant evidences suggesting their potential benefit on bone healing, there are some evidences showing their side effects such as ectopic bone formation, osteolysis and problems related to cost effectiveness. Bone tissue engineering may create a local environment, using the delivery systems, which enables BMPs to carry out their activities and to lower cost and complication rate associated with BMPs. This review represented the most important concepts and evidences regarding the role of BMPs on bone healing and regeneration from basic to clinical application. The major advantages and disadvantages of such biologic compounds together with the BMPs substitutes are also discussed.

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Inhibin α‐subunit inhibits BMP9‐induced osteogenic differentiation through blocking BMP/Smad signal and activating NF‐κB signal in mesenchymal stem cells

Huang

Cheng²,

Jitao³

et al. 2018

J of Cellular Biochemistry

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Inhibin-α, a member of the transforming growth factor (TGF-β) superfamily, has been involved in bone turnover during the menopausal transition via endocrine effects, and it was previously reported that inhibins may antagonize the function of BMPs. Certainly, one of the most important functions of BMPs is to induce osteogenic differentiation. BMP9 as one of the most potent BMPs to induce osteogenic differentiation has gotten more and more attentions. Nonetheless, the effects of inhibin-α on osteogenesis remain unknown. Besides, mesenchymal stem cells (MSCs) with the ability to differentiate into multiple mesenchymal lineages, including osteoblasts, adipocyte, chondrocytes, and myoblasts in vitro, have become the promising seed cells for bone tissue engineering. Here, we investigated the role of inhibin-α on BMP9-induced osteogenic differentiation in MSCs and tried to discover the mechanism underlying this process. We found inhibin-α apparently reduced the classical osteogenic markers and the ectopic bone formation induced by BMP9. In addition, the ratio of OPG to RANKL is declined also in the presence of inhibin-α. For mechanism, we found that exogenous expression of inhibin-α inhibits BMP9-induced osteogenic differentiation through blocking BMP/Smad signal transduction and activating NF-κB signal which is repressed by BMP9. Thus, our findings indicated that inhibin-α has a negative effect on BMP9-induced osteogenic differentiation in MSCs, which may provide a novel insight into the regulation of skeletal development and new strategy for bone tissue engineering.

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All-trans retinoic acid modulates bone morphogenic protein 9-induced osteogenesis and adipogenesis of preadipocytes through BMP/Smad and Wnt/β-catenin signaling pathways

Cited by 59 publications

References 47 publications

Transdifferentiation of adipocytes to osteoblasts: potential for orthopaedic treatment

Transdifferentiation of adipocytes to osteoblasts: potential for orthopaedic treatment

Bone morphogenetic proteins: A powerful osteoinductive compound with non‐negligible side effects and limitations

Inhibin α‐subunit inhibits BMP9‐induced osteogenic differentiation through blocking BMP/Smad signal and activating NF‐κB signal in mesenchymal stem cells

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