Suppression of p38α MAPK Signaling in Osteoblast Lineage Cells Impairs Bone Anabolic Action of Parathyroid Hormone

Thouverey, Cyril; Caverzasio, Joseph

doi:10.1002/jbmr.2762

Cited by 21 publications

(13 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the authors reported that, in these animals, PTH-induced expression of Rankl is supressed, still the net effect of p38 deletion is reduced ossification, due to the inability of PTH to induce osteogenic genes. In addition, the authors establish the possibility that PTH activates p38 through cAMP/PKA signaling (Thouverey and Caverzasio, 2015b ). Mechanistically, it has been proposed that PTH increases both SMAD and p38 BMP signaling in MSCs (Yu et al, 2012 ).…”

Section: Signaling Triggers P38 In Osteoblast Functionmentioning

confidence: 95%

p38 MAPK Signaling in Osteoblast Differentiation

Rodríguez-Carballo

Gámez

Ventura

2016

Front. Cell Dev. Biol.

243

184

View full text Add to dashboard Cite

The skeleton is a highly dynamic tissue whose structure relies on the balance between bone deposition and resorption. This equilibrium, which depends on osteoblast and osteoclast functions, is controlled by multiple factors that can be modulated post-translationally. Some of the modulators are Mitogen-activated kinases (MAPKs), whose role has been studied in vivo and in vitro. p38-MAPK modifies the transactivation ability of some key transcription factors in chondrocytes, osteoblasts and osteoclasts, which affects their differentiation and function. Several commercially available inhibitors have helped to determine p38 action on these processes. Although it is frequently mentioned in the literature, this chemical approach is not always as accurate as it should be. Conditional knockouts are a useful genetic tool that could unravel the role of p38 in shaping the skeleton. In this review, we will summarize the state of the art on p38 activity during osteoblast differentiation and function, and emphasize the triggers of this MAPK.

show abstract

Section: Signaling Triggers P38 In Osteoblast Functionmentioning

confidence: 95%

p38 MAPK Signaling in Osteoblast Differentiation

Rodríguez-Carballo

Gámez

Ventura

2016

Front. Cell Dev. Biol.

243

184

View full text Add to dashboard Cite

show abstract

“…Primary osteoblast were isolated from long bones of Pdgfra f/f ; Pdgfrb f/f mice as previously described. (24) Briefly, bone chips were prepared from cleaned long bones and digested in 1 mg/mL collagenase II (Sigma) for 90 minutes at 37 C. Bone pieces were washed several times and incubated in α-MEM (Amimed, Bioconcept, Salem, NH, USA) containing 10% FBS (Gibco) for 9 days to allow cell migration from bone fragments. At that point, cells and bone chips were trypsinized (with trypsin/EDTA from Sigma) and passaged at a split ratio of 1:3.…”

Section: Osteoblast Culturesmentioning

confidence: 99%

PDGF Receptor Signaling in Osteoblast Lineage Cells Controls Bone Resorption Through Upregulation of Csf1 Expression

Brun

Andreasen

Ejersted

et al. 2020

Journal of Bone and Mineral Research

Self Cite

View full text Add to dashboard Cite

The physiological functions of platelet‐derived growth factor receptors (PDGFRs) α and β in osteoblast biology and bone metabolism remain to be established. Here, we show that PDGFRA and PDGFRB genes are expressed by osteoblast‐lineage canopy and reversal cells in close proximity to PDGFB‐expressing osteoclasts within human trabecular bone remodeling units. We also report that, although removal of only one of the two PDGFRs in Osterix‐positive cells does not affect bone phenotype, suppression of both PDGFRs in those osteoblast lineage cells increases trabecular bone volume in male mice as well as in female gonad‐intact and ovariectomized mice. Furthermore, osteoblast lineage‐specific suppression of PDGFRs reduces Csf1 expression, bone marrow level of macrophage colony‐stimulating factor (M‐CSF), number of osteoclasts, and, therefore, bone resorption, but does not change bone formation. Finally, abrogation of PDGFR signaling in osteoblasts blocks PDGF‐induced ERK1/2‐mediated Csf1 expression and M‐CSF secretion in osteoblast cultures and calcitriol‐mediated osteoclastogenesis in co‐cultures. In conclusion, our results indicate that PDGFR signaling in osteoblast lineage cells controls bone resorption through ERK1/2‐mediated Csf1 expression. © 2020 American Society for Bone and Mineral Research (ASBMR).

show abstract

“…Osteoblasts were isolated from long bones of Ocy-PPARg 2/2 and Ocy-PPARg +/+ mice as previously described (22). Osteoblasts were seeded at 60,000 cells per well in 12-well plates.…”

Section: Primary Osteoblast Culturesmentioning

confidence: 99%

“…To investigate the proof of concept that deletion of PPARg in bone cells is able to prevent hepatic steatosis, improve FA metabolism by adipocytes, and augment pancreatic islet insulin secretion, we applied CM or performed real cocultures of mature osteoblasts with hepatocytes, adipocytes, and pancreatic b-cells. For this purpose, primary OB-OCY of Ocy-PPARg 2/2 and Ocy-PPARg +/+ were extracted from long bones as previously described (22). After 21 days of culture, CM was collected and added to primary hepatocytes from WT mice incubated with a mix of oleate and palmitate for 48 h to induce steatosis (Fig.…”

Section: Osteokines Secreted By Ocy-pparg 2/2 Mice Control Adipose Lmentioning

confidence: 99%

Bone Regulates Browning and Energy Metabolism Through Mature Osteoblast/Osteocyte PPARγ Expression

et al. 2017

View full text Add to dashboard Cite

Peroxisome proliferator-activated receptor γ (PPARγ) is a master regulator of energy metabolism. In bone, it is known to regulate osteoblast differentiation and osteoclast activity. Whether PPARγ expression in bone cells, particularly osteocytes, regulates energy metabolism remains unknown. Here, we show that mature osteoblast/osteocyte-specific ablation of PPARγ in mice (γ/) alters body composition with age, namely, to produce less fat and more lean mass, and enhances insulin sensitivity and energy expenditure compared with wild-type mice. In addition, γ mice exhibit more bone density, structure, and strength by uncoupling bone formation from resorption. When challenged with a high-fat diet, γ mice retain glycemic control, with increased browning of the adipose tissue, decreased gluconeogenesis, and less hepatic steatosis. Moreover, these metabolic effects, particularly an increase in fatty acid oxidation, cannot be explained by decarboxylated osteocalcin changes, suggesting existence of other osteokines that are under the control of PPARγ. We further identify bone morphogenetic protein 7 as one of them. Hence, osteocytes coregulate bone and glucose homeostasis through a PPARγ regulatory pathway, and its inhibition could be clinically relevant for the prevention of glucose metabolic disorders.

show abstract

Suppression of p38α MAPK Signaling in Osteoblast Lineage Cells Impairs Bone Anabolic Action of Parathyroid Hormone

Cited by 21 publications

References 35 publications

p38 MAPK Signaling in Osteoblast Differentiation

p38 MAPK Signaling in Osteoblast Differentiation

PDGF Receptor Signaling in Osteoblast Lineage Cells Controls Bone Resorption Through Upregulation of Csf1 Expression

Bone Regulates Browning and Energy Metabolism Through Mature Osteoblast/Osteocyte PPARγ Expression

Contact Info

Product

Resources

About