Activation of Peroxisome Proliferator-activated Receptor-γ Pathway Inhibits Osteoclast Differentiation

Mbalaviele, Gabriel; Abu‐Amer, Yousef; Meng, Alice; Jaiswal, Rama K.; Beck, Steve; Pittenger, Mark F.; Thiede, Mark A.; Marshak, Daniel R.

doi:10.1074/jbc.275.19.14388

Cited by 104 publications

(85 citation statements)

References 36 publications

(47 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…There exists a major discrepancy regarding the role of PPARg in osteoclastogenesis. Previous in vitro studies showed that PPARg agonists inhibit osteoclastogenesis via NF-kB, (53) NFATc1, (54) or mitogen-activated protein (MAP) kinase pathway (55) in osteoclast precursors. In contrast, osteoclast-specific deletion of PPARg has resulted in osteopetrotic phenotype with compromised RANKL signaling and osteoclast differentiation, indicating that PPARg in fact has a pro-osteoclastic potential.…”

Section: Discussionmentioning

confidence: 99%

Osteoblast-targeted overexpression of PPARγ inhibited bone mass gain in male mice and accelerated ovariectomy-induced bone loss in female mice

Cho

Yang

Her

et al. 2011

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

PPARg has critical role in the differentiation of mesenchymal stem cells into adipocytes while suppressing osteoblastic differentiation. We generated transgenic mice that overexpress PPARg specifically in osteoblasts under the control of a 2.3-kb procollagen type 1 promoter (Col.1-PPARg). Bone mineral density (BMD) of 6-to 14-week-old Col.1 À PPARg male mice was 8% to 10% lower than that of their wildtype littermates, whereas no difference was noticed in Col.1-PPARg female mice. Col.1-PPARg male mice exhibited decreased bone volume (45%), trabecular thickness (23%), and trabecular number (27%), with a reciprocal increase in trabecular spacing (51%). Dynamic histomorphometric analysis also revealed that bone-formation rate (42%) and mineral apposition rate (32%) were suppressed significantly in Col.1-PPARg male mice compared with their wild-type littermates. Interestingly, osteoclast number and surface also were decreased by 40% and 58%, respectively, in Col.1-PPARg male mice. In vitro whole-marrow culture for osteoclastogenesis also showed a significant decrease in osteoclast formation (approximately 35%) with the cells from Col.1-PPARg male mice, and OPG/RANKL ratio was reduced in stromal cells from Col.1-PPARg male mice. Although there was no significant difference in BMD in Col.1-PPARg female mice up to 30 weeks, bone loss was accelerated after ovariectomy compared with wild-type female mice (À3.9% versus À6.8% at 12 weeks after ovariectomy, p < .01), indicating that the effects of PPARg overexpression becomes more evident in an estrogen-deprived state in female mice. In conclusion, in vivo osteoblast-specific overexpression of PPARg negatively regulates bone mass in male mice and accelerates estrogen-deficiency-related bone loss in female mice. ß

show abstract

Section: Discussionmentioning

confidence: 99%

Osteoblast-targeted overexpression of PPARγ inhibited bone mass gain in male mice and accelerated ovariectomy-induced bone loss in female mice

Cho

Yang

Her

et al. 2011

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

show abstract

“…Mbalaviele et al (2000) showed that the activation of PPAR-γ pathway by an endogenous PPAR-γ ligand, blocked the effects of OPG ligand and thus, inhibited the formation and activity of osteoclasts in human mesenchymal stem cells through the inhibition of receptor-activated NF-κB ligand (RANKL) blocking the NF-κB pathway. Okazaki et al (1999) similarly reported that the thiazolidindione treatment decreased the number of osteoclast-like cells induced by 1,25-(OH)2D3 or PTH, suggesting the inhibitory role of PPAR-γ activation on bone resorption.…”

Section: Discussionmentioning

confidence: 99%

“…Very recent work by Chan et al (2007) demonstrated that PPAR-γ agonist added to human peripheral blood mononuclear cells culture resulted in significant dose-dependent inhibition of multinucleated osteoclast formation. Although the precise mechanisms regarding the association of PPAR-γ and osteoclastogenesis are not clarified, the antagonistic effects of PPAR-γ on the transcription factor NF-κB, which is the fundamental pathway for RANKL signaling and essential for osteoclast development, survival and function, and the subsequent association of osteoprotegerin, a critical inhibitory factor in osteoclastogenesis, are suggested (Mbalaviele et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Based on the fact that osteo-blasts and adipocytes share a common mesenchymal precursor, recent studies have demonstrated that the activation of PPAR-γ stimulated adipocyte differentiation and simultaneously blocked their ability to differentiate into osteoblasts or promoted their apoptosis (Nuttall et al, 1998;Lecka-Czernik et al, 1999Rosen and Spiegelman, 2001;Sorocéanu et al, 2004). In addition, PPAR-γ activation seems to have regulatory effects on bone metabolism through regulating their differentiation or activation into osteoclasts (Okazaki et al, 1999;Mbalaviele et al, 2000;Chan et al, 2007). However, the evidences on whether PPAR-γ activation might affect bone metabolism through activation or inhibition of either cell lineages are not enough to draw a conclusion.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The association of Pro12Ala polymorphism of peroxisome proliferator-activated receptor-γ gene with serum osteoprotegerin levels in healthy Korean women

Rhee

Oh²,

Yun³

et al. 2007

Exp Mol Med

View full text Add to dashboard Cite

Recent evidences suggest that the activation of peroxisome proliferator-activated receptor (PPAR)-γ, which is an important transcriptional factor in adipocyte differentiation, also plays an important role in the bone microenvironment. The objective of the study was to clarify whether Pro12Ala polymorphism was related to the serum OPG levels and bone mineral metabolism in healthy Korean women. In 239 Korean women (mean age 51 years), who participated in medical check-up program in a health promotion center, anthropometric measurements, lumbar spine and femoral neck bone mineral density (BMD), bone turnover markers, such as serum total alkaline phosphatase (ALP) levels, urine deoxypyridinoline levels, and 24-h urine calcium excretion were measured. Serum levels of OPG were measured with ELISA method. DNAs were extracted from the samples and the genotyping of the Pro12Ala polymorphism (rs1801282) in the PPAR-γ gene was performed via an allelic discrimination assay using a TaqMan probe. In addition, we examined the haplotype analysis between two polymorphisms of PPAR-γ gene, Pro12Ala in exon B and C161T in exon 6 (rs3856806). Allelic frequencies were 0.950 for Pro allele and 0.050 for Ala allele, which was in compliance with HardyWeinberg equilibrium, and there was no Ala12Ala genotype among the genotyped subjects. Mean serum OPG level was significantly lower (P = 0.035), and serum total ALP was significantly higher (P = 0.014) in the Pro12Ala genotype group compared with the Pro12Pro genotype group, which were consistently significant even after adjustment for weight, height, and serum follicle stimulating hormone (FSH). In multiple regression analysis with serum OPG as the dependent variable and age, weight, ALP, femoral neck BMD and Pro12Ala genotype included in the model, only Pro12Ala genotype was significant determinant of serum OPG level (β = 0.136, P = 0.035). The haplotype analysis with C161T polymorphism revealed that subjects with Ala and T alleles showed significantly lower serum OPG levels compared with those with Pro12Pro/CC genotype, which were consistently significant even after adjustment for age, weight, height and FSH (P = 0.010). This result suggests statistically significant association of Pro12Ala polymorphisms with serum OPG levels in Korean females.

show abstract

“…Peroxisome proliferator-activated receptor (PPAR)-γ belongs to the nuclear hormone receptor family, which is predominantly expressed in the adipose tissue, and also plays an important role in the bone micro environment (6). In addition, PPAR-γ activation seems to have regulatory effects on bone metabolism through regulating their differentiation or activation into osteoclasts (7)(8)(9). However, evidence on whether the activation of PPAR-γ may affect bone metabolism through the activation or inhibition or cell lineages is not enough for conclusion.…”

Section: Introductionmentioning

confidence: 99%

No Association Between His 447 His Polymorphism of Pparγ Gene and Osteoporosis in Iranian Postmenopausal Women

Sahmani¹,

Azizi²,

Javadi³

et al. 2017

Biotech Health Sci

View full text Add to dashboard Cite

Background: Osteoporosis is frequently observed in postmenopausal women. Evidence indicates that the role of genetic factors is significant in osteoporosis. This study aimed to inspect the potential association between His 447 His polymorphism of PPARγ gene and bone mineral density (BMD) and serum lipid profiles in postmenopausal women suffering from osteoporosis compared to the healthy controls.

show abstract

Activation of Peroxisome Proliferator-activated Receptor-γ Pathway Inhibits Osteoclast Differentiation

Cited by 104 publications

References 36 publications

Osteoblast-targeted overexpression of PPARγ inhibited bone mass gain in male mice and accelerated ovariectomy-induced bone loss in female mice

Osteoblast-targeted overexpression of PPARγ inhibited bone mass gain in male mice and accelerated ovariectomy-induced bone loss in female mice

The association of Pro12Ala polymorphism of peroxisome proliferator-activated receptor-γ gene with serum osteoprotegerin levels in healthy Korean women

No Association Between His 447 His Polymorphism of Pparγ Gene and Osteoporosis in Iranian Postmenopausal Women

Contact Info

Product

Resources

About