Signal transduction by basic fibroblast growth factor in rat osteoblastic py1a cells

Hurley, Marja M.; Marcello, K.; Abreu, Christine; Kessler, Michael

doi:10.1002/jbmr.5650110910

Cited by 45 publications

(11 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have been particularly interested in this latter control mechanism and showed that ERK1/2 MAPK‐dependent phosphorylation of RUNX2 is critical for osteoblast‐specific gene expression and differentiation 8, 9. This pathway mediates the response of bone cells to a variety of signals including hormone/growth factor stimulation,10, 11 extracellular matrix binding/matrix tension,12–15 and mechanical loading 16, 17. ERK1/2 phosphorylates four serine residues on RUNX2 (S43, S301, S319, and S510, using the amino acid residue numbering for murine Type II RUNX2 isoform having N‐terminal sequence MASN) 18.…”

Section: Introductionmentioning

confidence: 99%

Interactions between extracellular signal-regulated kinase 1/2 and P38 Map kinase pathways in the control of RUNX2 phosphorylation and transcriptional activity

Yang

Zhao

et al. 2011

Journal of Bone and Mineral Research

141

123

View full text Add to dashboard Cite

RUNX2, a key transcription factor for osteoblast differentiation, is regulated by ERK1/2 and p38 MAP kinase-mediated phosphorylation. However, the specific contribution of each kinase to RUNX2-dependent transcription is not known. Here we investigate ERK and p38 regulation of RUNX2 using a unique P-RUNX2-specific antibody. Both MAP kinases stimulated RUNX2 Ser319 phosphorylation and transcriptional activity. However, a clear preference for ERK1 versus p38α/β was seen when the ability of these MAPKs to phosphorylate and activate RUNX2 was compared. Similarly, ERK1 preferentially bound to a consensus MAPK binding site on RUNX2 that was essential for the activity of either kinase. To assess the relative contribution of ERK1/2 and p38 to osteoblast gene expression, MC3T3-E1 preosteoblast cells were grown in control or ascorbic acid (AA)-containing medium ± BMP2/7. AA-induced gene expression, which requires collagen matrix synthesis, was associated with parallel increases in P-ERK and RUNX2-S319-P in the absence of any changes in P-p38. This response was blocked by ERK, but not p38, inhibition. Significantly, in the presence of AA, BMP2/7 synergistically stimulated RUNX2 S319 phosphorylation and transcriptional activity without affecting total RUNX2 and this response was totally dependent on ERK/MAPK activity. In contrast, although p38 inhibition partially blocked BMP-dependent transcription, it did not affect RUNX2 S319 phosphorylation, suggesting the involvement of other phosphorylation sites and/or transcription factors in this response. Based on this work, we conclude that extracellular matrix and BMP regulation of RUNX2 phosphorylation and transcriptional activity in osteoblasts is predominantly mediated by ERK rather than p38 MAPKs.

show abstract

Section: Introductionmentioning

confidence: 99%

Interactions between extracellular signal-regulated kinase 1/2 and P38 Map kinase pathways in the control of RUNX2 phosphorylation and transcriptional activity

Yang

Zhao

et al. 2011

Journal of Bone and Mineral Research

141

123

View full text Add to dashboard Cite

show abstract

“…(39,49,50) In OBs, the ERK pathway is a major conduit for conveying information from the extracellular environment to the nucleus, and has been implicated in the response of OBs to a variety of signals, including hormone/ growth factor stimulation, extracellular matrix-integrin binding, and mechanical loading. (51)(52)(53) ERK activation stimulates OB differentiation and skeletal development through OBs' essential transcription factor, Runx2, which plays an important role during the process. (54,55) Our results are in agreement with these findings.…”

Section: Discussionmentioning

confidence: 99%

Regulator of G Protein Signaling Protein 12 (Rgs12) Controls Mouse Osteoblast Differentiation via Calcium Channel/Oscillation and Gαi-ERK Signaling

Liu

Gilmore

et al. 2018

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

Bone homeostasis intimately relies on the balance between osteoblasts (OBs) and osteoclasts (OCs). Our previous studies have revealed that regulator of G protein signaling protein 12 (Rgs12), the largest protein in the Rgs super family, is essential for osteoclastogenesis from hematopoietic cells and OC precursors. However, how Rgs12 regulates OB differentiation and function is still unknown. To understand that, we generated an OB‐targeted Rgs12 conditional knockout (CKO) mice model by crossing Rgs12fl/fl mice with Osterix (Osx)‐Cre transgenic mice. We found that Rgs12 was highly expressed in both OB precursor cells (OPCs) and OBs of wild‐type (WT) mice, and gradually increased during OB differentiation, whereas Rgs12‐CKO mice (OsxCre/+; Rgs12fl/fl) exhibited a dramatic decrease in both trabecular and cortical bone mass, with reduced numbers of OBs and increased apoptotic cell population. Loss of Rgs12 in OPCs in vitro significantly inhibited OB differentiation and the expression of OB marker genes, resulting in suppression of OB maturation and mineralization. Further mechanism study showed that deletion of Rgs12 in OPCs significantly inhibited guanosine triphosphatase (GTPase) activity and cyclic adenosine monophosphate (cAMP) level, and impaired Calcium (Ca2+) oscillations via restraints of major Ca2+ entry sources (extracellular Ca2+ influx and intracellular Ca2+ release from endoplasmic reticulum), partially contributed by the blockage of L‐type Ca2+ channel mediated Ca2+ influx. Downstream mediator extracellular signal‐related protein kinase (ERK) was found inactive in OBs of OsxCre/+; Rgs12fl/fl mice and in OPCs after Rgs12 deletion, whereas application of pertussis toxin (PTX) or overexpression of Rgs12 could rescue the defective OB differentiation via restoration of ERK phosphorylation. Our findings reveal that Rgs12 is an important regulator during osteogenesis and highlight Rgs12 as a potential therapeutic target for bone disorders. © 2018 American Society for Bone and Mineral Research.

show abstract

“…ERK pathway represents an important signaling involved in osteogenesis [46, 47]. In bone, ERKs promote the proliferation and differentiation of osteoblasts [43, 48], and mediates the response of bone to a variety of stimuli, including hormone/growth factor stimulation [49, 50], extracellular matrix–integrin binding [51] and mechanical loading [52]. In particular, ERK phosphorylates RUNX2, thus enhancing RUNX2 dependent gene expression [15–19, 46, 47, 53].…”

Section: Discussionmentioning

confidence: 99%

Betaine promotes cell differentiation of human osteoblasts in primary culture

Villa¹,

Senesi

Montesano

et al. 2017

J Transl Med

View full text Add to dashboard Cite

BackgroundBetaine (BET), a component of many foods, is an essential osmolyte and a source of methyl groups; it also shows an antioxidant activity. Moreover, BET stimulates muscle differentiation via insulin like growth factor I (IGF-I). The processes of myogenesis and osteogenesis involve common mechanisms with skeletal muscle cells and osteoblasts sharing the same precursor. Therefore, we have hypothesized that BET might be effective on osteoblast cell differentiation.MethodsThe effect of BET was tested in human osteoblasts (hObs) derived from trabecular bone samples obtained from waste material of orthopedic surgery. Cells were treated with 10 mM BET at 5, 15, 60 min and 3, 6 and 24 h. The possible effects of BET on hObs differentiation were evaluated by real time PCR, western blot and immunofluorescence analysis. Calcium imaging was used to monitor intracellular calcium changes.ResultsReal time PCR results showed that BET stimulated significantly the expression of RUNX2, osterix, bone sialoprotein and osteopontin. Western blot and immunofluorescence confirmed BET stimulation of osteopontin protein synthesis. BET stimulated ERK signaling, key pathway involved in osteoblastogenesis and calcium signaling. BET induced a rise of intracellular calcium by means of the calcium ions influx from the extracellular milieu through the L-type calcium channels and CaMKII signaling activation. A significant rise in IGF-I mRNA at 3 and 6 h and a significant increase of IGF-I protein at 6 and 24 h after BET stimulus was detected. Furthermore, BET was able to increase significantly both SOD2 gene expression and protein content.ConclusionsOur study showed that three signaling pathways, i.e. cytosolic calcium influx, ERK activation and IGF-I production, are enhanced by BET in human osteoblasts. These pathways could have synergistic effects on osteogenic gene expression and protein synthesis, thus potentially leading to enhanced bone formation. Taken together, these results suggest that BET could be a promising nutraceutical therapeutic agent in the strategy to counteract the concomitant and interacting impact of sarcopenia and osteoporosis, i.e. the major determinants of senile frailty and related mortality.

show abstract

Signal transduction by basic fibroblast growth factor in rat osteoblastic py1a cells

Cited by 45 publications

References 29 publications

Interactions between extracellular signal-regulated kinase 1/2 and P38 Map kinase pathways in the control of RUNX2 phosphorylation and transcriptional activity

Interactions between extracellular signal-regulated kinase 1/2 and P38 Map kinase pathways in the control of RUNX2 phosphorylation and transcriptional activity

Regulator of G Protein Signaling Protein 12 (Rgs12) Controls Mouse Osteoblast Differentiation via Calcium Channel/Oscillation and Gαi-ERK Signaling

Betaine promotes cell differentiation of human osteoblasts in primary culture

Contact Info

Product

Resources

About