Bone morphogenetic protein 9 stimulates callus formation in osteoporotic rats during fracture healing

Wang, Xing; Huang, Jun; Fan, Huang; Zong, Jingfeng; Tang, Xi; Yang, Liu; Zhang, Qiong‐Fang; Wang, Yang; Chen, Liang; Liang, Yin; Deng, Zhong‐Liang

doi:10.3892/mmr.2017.6302

Cited by 15 publications

(11 citation statements)

References 34 publications

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“…BMP9, which belongs to the TGF-β superfamily, can induce MSCs, such as mouse embryonic fibroblasts (MEFs) or C3H10 cells, to differentiate into bone tissue [17,22,23,71,72]. Further, MSC-to-osteoblast transition is driven by BMP9, the most potent osteogenesis-inducing BMP signal in vitro and in vivo [21,22,73].…”

Section: Discussionmentioning

confidence: 99%

“…Real-time PCR results confirmed that our adenovirus stably overexpresses BMP9 in GC-1spg cells. Secondly, expression of osteogenic markers, including OPN, OCN, Sox9, and Runx2 [17,38,62,65,71,80], is enhanced by BMP9 in GC-1spg cells. Furthermore, ALP and mineralized calcium nodules, early osteogenesis markers, are increased by BMP9 overexpression.…”

Section: Discussionmentioning

confidence: 99%

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Bone morphogenetic protein 9 induces osteogenic differentiation of germ cell 1 spermatogonial cells

Zhang

Xu²,

Chen³

et al. 2019

Preprint

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30Germ cell 1 spermatogonial (GC-1spg) cells are multipotent progenitor cells. We 31 previously confirmed that bone morphogenetic protein (BMP) 9 is among the most 32 osteogenic BMPs. However, whether GC-1spg cells are driven toward osteogenic 33 differentiation under proper stimuli is uncertain. Additionally, the molecular 34 mechanism of BMP9 remains unclear. In the present study, we aimed to determine 35 whether BMP9 can induce osteogenic differentiation of GC-1spg cells. Recombinant 36 adenoviruses were generated by the AdEasy system to regulate the BMP9 expression in 37 GC-1spg cells. We identified osteogenic markers by real-time PCR and staining 38 techniques in vitro. Ectopic ossification assays and histological analysis were also 39 performed to verify the in vivo activity of BMP9. Finally, potential signaling pathways 40 of BMP9 were assessed by transcriptome sequencing and KEGG enrichment analysis. 41Using recombinant adenoviruses, we demonstrate that BMP9 upregulates osteogenic 42 markers including Runx2, osteocalcin, osteopontin, and Sox9. BMP9 also activates 43 alkaline phosphatase activity and calcium deposition in GC-1spg cells. In vivo results 44show that BMP9 overexpression in GC-1spg cells promotes ectopic bone formation and 45 chondrogenesis. In addition, RNA-sequencing and KEGG pathway analysis 3 46 demonstrate that several signaling pathways are involved in BMP9-mediated 47 osteogenesis. GC-1spg cells not only maintain spermatogenesis but also retain the 48 ability to form bone tissue. Therefore, BMP9 activity in GC-1spg cells may help 49 identify signaling pathways implicated in bone formation and could be of use in 50 regenerative medicine. 51 Keywords: Bone morphogenetic protein 9, RNA-seq, KEGG pathway analysis, 52 recombinant adenovirus, chondrogenesis 53 Introduction 54 Germ cell 1 spermatogonial (GC-1spg) cells are mouse spermatogonia that are 55 immortalized by the SV40 large T antigen [1]. These cells can differentiate into diverse cell 56 types or undergo self-renewal, depending on different factors [2,3,4]. GC-1spg cells are 57 largely involved in spermatogenesis and have mesenchymal stem cell (MSC) differentiation 58 potential [5,6,7,8]. In other words, GC-1spg cells can differentiate into different cell types, 59including those of the osteogenic, chondrogenic, or adipogenic lineages [9,10,11,12]. 60However, several molecular events [13,14] and factors are involved in osteogenic 61 differentiation of MSCs. Importantly, bone morphogenetic proteins (BMPs) are essential for 62 this process [15,16,17]. 63 BMPs, members of the TGF-β superfamily, are required for bone formation, stem cell 64 differentiation, and male reproduction [15,16,18,19,20]. Thus far, more than 15 different 65 BMPs have been identified. Our previous work showed that BMP9 is the most osteogenic 66 BMP [21,22,23,24]. BMP9, also known as growth differentiation factor 2 (GDF-2)[25], was 67 originally isolated from the fetal mouse liver [25,26]. Bone formation involves BMP9 acting 68 through the Notch signaling ...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Bone morphogenetic protein 9 induces osteogenic differentiation of germ cell 1 spermatogonial cells

Zhang

Xu²,

Chen³

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…A study implemented in an ovariectomy mouse model found that BMP9 attenuates bone loss and improves bone biomechanical properties in vivo by increasing bone-forming activity and suppressing bone resorption activity [ 32 ]. BMP9 is an important factor in bone formation [ 7 , 33 , 34 ]. BMP9 significantly mediated callus formation and increased bone mass and strength in osteoporotic rats [ 33 ].…”

Section: Bmps and Bonementioning

confidence: 99%

Potential Functions of the BMP Family in Bone, Obesity, and Glucose Metabolism

Chen

Wang³

et al. 2021

Journal of Diabetes Research

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Characteristic bone metabolism was observed in obesity and diabetes with controversial conclusions. Type 2 diabetes (T2DM) and obesity may manifest increased bone mineral density. Also, obesity is more easily to occur in T2DM. Therefore, we infer that some factors may be linked to bone and obesity as well as glucose metabolism, which regulate all of them. Bone morphogenetic proteins (BMPs), belonging to the transforming growth factor- (TGF-) beta superfamily, regulate a diverse array of cellular functions during development and in the adult. More and more studies revealed that there exists a relationship between bone metabolism and obesity as well as glucose metabolism. BMP2, BMP4, BMP6, BMP7, and BMP9 have been shown to affect the pathophysiological process of obesity and glucose metabolism beyond bone metabolism. They may exert functions in adipogenesis and differentiation as well as insulin resistance. In the review, we summarize the literature on these BMPs and their association with metabolic diseases including obesity and diabetes.

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“…BMSCs are pluripotent stromal cells that are easily isolated and cultured in vitro, 8,9 which has osteogenic differentiation potential, and strong proliferative capacity. [10][11][12] It has been demonstrated in many studies that BMSCs plays an important role in bone formation 13 and is therefore considered to be a good seed cell for bone tissue engineering, 14 as well as one of the most important cellular sources of regenerative medicine. 15 The methods of obtaining BMSCs mainly include flow cytometry separation, whole bone marrow culture and density gradient centrifugation combined with adherent culture.…”

Section: Discussionmentioning

confidence: 99%

Effects of lentiviral transfection containing bFGF gene on the biological characteristics of rabbit BMSCs

Peng

Zhang

et al. 2018

J of Cellular Biochemistry

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To investigate the effect of lentiviral transfection containing bFGF gene on the biological characteristics of bone marrow stromal cells (BMSCs). BMSCs were obtained by density gradient centrifugation and adherence screening. The bFGF gene was transfected into BMSCs by lentiviral vector and divided into bFGF transfection group, empty virus group, and untransfected group according to the transfection conditions. After transfection, the morphology, expression of bFGF mRNA and protein, cell proliferation, cell cycle, and alkaline phosphatase (ALP) activity were observed in three groups of cells. High density BMSCs were successfully obtained by density gradient centrifugation and adherence screening. After transfection of BMSCs with bFGF gene, the cell morphology did not change significantly, while the expression of bFGF mRNA and protein were significantly increased, the cell proliferation curve shifted upward, the proportion of proliferating cells increased, and the activity of ALP was significantly enhanced. Compared with empty virus group and untransfected group, there was significant difference (P < 0.05). The rabbit bFGF gene was successfully introduced into the BMSCs cultured in vitro by lentiviral vector, and the target gene was stably expressed. And the expression of bFGF can promote the proliferation and osteogenic differentiation of BMSCs.

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Bone morphogenetic protein 9 stimulates callus formation in osteoporotic rats during fracture healing

Cited by 15 publications

References 34 publications

Bone morphogenetic protein 9 induces osteogenic differentiation of germ cell 1 spermatogonial cells

Bone morphogenetic protein 9 induces osteogenic differentiation of germ cell 1 spermatogonial cells

Potential Functions of the BMP Family in Bone, Obesity, and Glucose Metabolism

Effects of lentiviral transfection containing bFGF gene on the biological characteristics of rabbit BMSCs

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