BMP‐2 regulation of PTHrP and osteoclastogenic factors during osteoblast differentiation of C2C12 cells

Susperregui, Antonio R.G.; Viñals, Francesc; Ho, Patricia W. M.; Gillespie, Matthew T.; Martın, Thomas; Ventura, Francesc

doi:10.1002/jcp.21389

Cited by 31 publications

(33 citation statements)

References 53 publications

(66 reference statements)

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“…As discussed earlier, muscle progenitor cells exposed to appropriate cues are permissive to committing toward an osteogenic lineage. It is known that BMP can induce an osteoblast phenotype even in the C2C12 model used in our studies (125)(126)(127)(128)(129)(130)(131)(132). Moreover, we have also recently reported that down-regulation of the Men-1 gene product (Menin) is a prerequisite to myogenesis, and maintenance of its expression favors osteoblast, rather than myoblast, commitment in multipotent mesenchymal cells such as C2C12 and C3H10T1/2 cell lines (106).…”

Section: Discussionmentioning

confidence: 63%

Identification of Differentially Regulated Secretome Components During Skeletal Myogenesis

Chan

Masui

Krakovska

et al. 2011

Molecular & Cellular Proteomics

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Myogenesis is a well-characterized program of cellular differentiation that is exquisitely sensitive to the extracellular milieu. Systematic characterization of the myogenic secretome (i.e. the ensemble of secreted proteins) is, therefore, warranted for the identification of novel secretome components that regulate both the pluripotency of these progenitor mesenchymal cells, and also their commitment and passage through the differentiation program. Previously, we have successfully identified 26 secreted proteins in the mouse skeletal muscle cell line C2C12 (1). In an effort to attain a more comprehensive picture of the regulation of myogenesis by its extracellular milieu, quantitative profiling employing stable isotope labeling by amino acids in cell culture was implemented in conjunction with two parallel high throughput online reverse phase liquid chromatography-tandem mass spectrometry systems.In summary, 34 secreted proteins were quantified, 30 of which were shown to be differentially expressed during muscle development. Intriguingly, our analysis has revealed several novel up-and down-regulated secretome components that may have critical biological relevance for both the maintenance of pluripotency and the passage of cells through the differentiation program. In particular, the altered regulation of secretome components, including follistatin-like protein-1, osteoglycin, spondin-2, and cytokine-induced apoptosis inhibitor-1, along with consti-

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Section: Discussionmentioning

confidence: 63%

Identification of Differentially Regulated Secretome Components During Skeletal Myogenesis

Chan

Masui

Krakovska

et al. 2011

Molecular & Cellular Proteomics

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“…Osteoblasts secrete PTHrP and express its receptor , and increasing evidence suggests that PTHrP may be an important local regulator of mesenchymal cell commitment and osteoblast activity (Chan et al, 2003;Martin, 2005;Goltzman, 2008). The effects of PTHrP on osteoblasts in vitro are known to vary with the culture conditions (Isogai et al, 1996;Ishizuya et al, 1997), but the majority of studies have shown that continuous exposure to PTHrP inhibits osteoblastic differentiation, although this may be mediated by PKA (Isogai et al, 1996;Susperregui et al, 2008), PKC (Miao et al, 2001), or both pathways (Ishizuya et al, 1997). In the present study PTHrP strongly suppressed ALP activity in osteoblasts, while PKA pathway activation slightly suppressed it, suggesting that PTHrP induces additional pathways to regulate ALP activity.…”

Section: Discussionmentioning

confidence: 98%

In vitro regulation of proliferation and differentiation within a postnatal growth plate of the cranial base by parathyroid hormone‐related peptide (PTHrP)

Wealthall

2009

Journal Cellular Physiology

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Parathyroid hormone-related peptide (PTHrP) is known to be an important regulator of chondrocyte differentiation in embryonic growth plates, but little is known of its role in postnatal growth plates. The present study explores the role of PTHrP in regulating postnatal chondrocyte differentiation using a novel in vitro organ culture model based on the ethmoidal growth plate of the cranial base taken from the postnatal day 10 mouse. In vitro the ethmoidal growth plate continued to mineralize and the chondrocytes progressed to hypertrophy, as observed in vivo, but the proliferative zone was not maintained. Treatment with PTHrP inhibited mineralization and reduced alkaline phosphatase (ALP) activity in the hypertrophic zone in the ethmoidal growth plates grown ex vivo, and also increased the proliferation of non-hypertrophic chondrocytes. In addition, exogenous PTHrP reduced the expression of genes associated with terminal differentiation: type X collagen, Runx2, and ALP, as well as the PTH/PTHrP receptor (PPR). Activation of the protein kinase A pathway using 8-Br-cAMP mimicked some of these pro-proliferative/anti-differentiative effects of PTHrP. PTHrP and PPR were found to be expressed within the ethmoidal growth plate using semi-quantitative PCR, and in other cranial growth plates such as the spheno-occipital and pre-sphenoidal synchondroses. These results provide the first functional evidence that PTHrP regulates proliferation and differentiation within the postnatal, cranial growth plate. J. Cell. Physiol. 219: 688-697, 2009. (c) 2009 Wiley-Liss, Inc.

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“…Under normal circumstances, pluripotent muscle-derived C2C12 cells develop and differentiate into muscle cells, however treatment with BMP-2 causes them to differentiate into osteoblasts (36). Thus, C2C12 cells have been widely used to study osteoblast differentiation in early stage.…”

Section: Discussionmentioning

confidence: 99%

Triptolide inhibits the function of TNF-α in osteoblast differentiation by inhibiting the NF-κB signaling pathway

Liu

Wang

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Chronic inflammation often delays fracture healing or leads to bone nonunion. Effectively suppressing pathological inflammation is crucial for fracture healing or bone remodeling. Triptolide, which is a diterpenoid epoxide, is the major active component of the Thunder God Vine, Tripterygium wilfordii. The aim of the present study was to investigate the role of triptolide in osteoblast differentiation and explore the molecular mechanisms of triptolide in fracture healing. Alkaline phosphatase (ALP) activity was used to evaluate osteoblast differentiation. ALP activity was measured via histochemical staining and western blotting was used to determine the expression of factors associated with inflammation. C2C12 cells were initially treated with 200 ng/ml bone morphogenetic protein (BMP)-2 alone for 3 days, which caused a significant increase in ALP activity (P<0.01). However, treatment with tumor necrosis factor (TNF)-α significantly decreased the ALP activity (P<0.05). Notably, treatment with the chronic inflammatory cytokine TNF-α significantly decreased the effect of BMP-2 in C2C12 cells compared with BMP-2 treatment alone (P<0.01). C2C12 cells were treated with increasing concentrations of BMP-2 or TNF-α for 3 days. The results demonstrated that TNF-α treatment significantly inhibited BMP-2-induced osteoblast differentiation in a dose-dependent manner (P<0.01). The role of triptolide in BMP-2-induced osteoblast differentiation was also examined. Cells were treated with BMP-2, BMP-2 + TNF-α alone, or BMP2 + TNF-α with increasing concentrations of triptolide (4, 8 or 16 ng/ml). After 3 days, the results of ALP activity revealed that triptolide significantly reversed the TNF-α-associated inhibition of osteoblast differentiation (P<0.01). Western blotting analysis demonstrated that triptolide markedly inhibited the phosphorylation of nuclear factor-κB, therefore suppressing the effects of TNF-α. In summary, triptolide is able to reverse the TNF-α-associated suppression of osteoblast differentiation, suggesting that triptolide treatment may have a positive effect on bone remodeling and fracture repairing.

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BMP‐2 regulation of PTHrP and osteoclastogenic factors during osteoblast differentiation of C2C12 cells

Cited by 31 publications

References 53 publications

Identification of Differentially Regulated Secretome Components During Skeletal Myogenesis

Identification of Differentially Regulated Secretome Components During Skeletal Myogenesis

In vitro regulation of proliferation and differentiation within a postnatal growth plate of the cranial base by parathyroid hormone‐related peptide (PTHrP)

Triptolide inhibits the function of TNF-α in osteoblast differentiation by inhibiting the NF-κB signaling pathway

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