Differential Roles of Smad1 and p38 Kinase in Regulation of Peroxisome Proliferator-activating Receptor γ during Bone Morphogenetic Protein 2-induced Adipogenesis

Hata, Kenji; Nishimura, Riko; Ikeda, Fumiyo; Yamashita, Kenji; Matsubara, Takuma; Nakamura, Takashi; Yoneda, Toshiyuki

doi:10.1091/mbc.e02-06-0356

Cited by 176 publications

(184 citation statements)

References 44 publications

Supporting

Mentioning

172

Contrasting

Order By: Relevance

“…Cont, control. (16,17), PPAR␥ binding element (PPRE)-luciferase construct (16), C/EBP␣ cDNA, C/EBP␤ cDNA (18), and C/EBP␦ cDNA (18) were kindly provided by Drs. Bruce M Spiegelman, Ormond MacDougald, and Shizuo Akira.…”

Section: Methodsmentioning

confidence: 99%

“…PPAR␥ promoter fused to a luciferase construct was used as described previously (19). Transfection of C3H10T1/2 cells was carried out using FuGENE 6 (Roche Applied Science) according to the manufacturer's protocol (17).…”

Section: Methodsmentioning

confidence: 99%

“…The adenovirus carrying Runx2 or PPAR␥ was used as described previously (17,20). The viruses showed no proliferative activity due to a lack of E1A-E1B (21).…”

Section: Methodsmentioning

confidence: 99%

“…After washing the cells twice with PBS and once with 60% isopropyl alcohol, the cells were stained with Oil Red-O solution (Sigma). The area of the cells stained with Oil Red-O was measured using an Image Pro Plus analyzer (Palmerton Inc.) (17).…”

Section: Fig 4 Induction Of Alp Activity By Msx2 In Runx2 Deficientmentioning

confidence: 99%

See 3 more Smart Citations

Reciprocal Roles of Msx2 in Regulation of Osteoblast and Adipocyte Differentiation

Ichida

Nishimura

Hata

et al. 2004

Journal of Biological Chemistry

Self Cite

176

132

View full text Add to dashboard Cite

Mice deficient in the Msx2 gene manifest defects in skull ossification and a marked reduction in bone formation associated with decreases in osteoblast numbers, thus suggesting that Msx2 is involved in bone formation. However, the precise role of Msx2 during osteoblast differentiation is not fully understood. In the present study, we investigated the role of Msx2 in the regulation of osteoblast differentiation in the multipotent mesenchymal cell lines C3H10T1/2 and C2C12 and in murine primary osteoblasts. Introduction of Msx2 induced alkaline phosphatase activity in C3H10T1/2 and C2C12 cells and promoted the calcification of murine primary osteoblasts. This effect of Msx2 was also ob- Differentiation and function of osteoblasts, which play an essential role in bone formation, are regulated by various hormones and cytokines, such as bone morphogenetic proteins (BMPs), 1 fibroblast growth factors, and the Wnt family (1, 2).These factors conduct the transcriptional events that are necessary for the differentiation process of osteoblasts. Runx2/ Cbfa1, an essential transcription factor for bone formation (1, 3), promotes the differentiation of undifferentiated mesenchymal cells into osteoblasts by regulating the transcription of type I collagen, osteopontin, and osteocalcin (4). A more recent study has shown that a zing finger transcription factor, Osterix, is necessary for bone formation and osteoblast differentiation (5). However, the molecular events that regulate the process of osteoblast differentiation have not been fully clarified.Msx2, a homeobox gene, is a mammalian homologue of the Drosophila muscle segment homeobox. Msx2 is known to be induced by BMPs, which play critical roles in bone formation and osteoblast differentiation (2). Msx2-deficient mice develop reduced bone formation, decreases in osteoblasts, impaired chondrogenesis, abnormal calvarial development, and defects in the ectodermal organs including the teeth, hair, and mammary glands (6). In contrast, transgenic mice overexpressing Msx2 show enhanced growth of calvariae (7). Mutations in the MSX2 gene in humans, which affects DNA binding activity, causes defects in skull ossification (8,9). Furthermore an autosomal dominant disorder, Boston-type craniosynostosis, results from a gain-of-function mutation of MSX2 at proline 148 (10, 11). These findings suggest a positive role for Msx2 in bone development and formation. In contrast to these genetic studies, in vitro studies have shown that Msx2 negatively regulates the transcription of the osteoblast-specific genes such as osteocalcin (12, 13). Furthermore Msx2 has been shown to bind to Runx2 and inhibit its transcriptional activity (14). These studies provide the notion that Msx2 serves as a negative regulator for osteoblast differentiation.To understand the complex role of Msx2 in osteoblast differentiation, we examined the effects of Msx2 on osteoblast differentiation of mesenchymal cells. We found that Msx2 promotes the differentiation of mesenchymal cells into the osteoblast lineage in a Runx...

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…The adenovirus carrying Runx2 or PPAR␥ was used as described previously (17,20). The viruses showed no proliferative activity due to a lack of E1A-E1B (21).…”

Section: Methodsmentioning

confidence: 99%

Section: Fig 4 Induction Of Alp Activity By Msx2 In Runx2 Deficientmentioning

confidence: 99%

See 2 more Smart Citations

Reciprocal Roles of Msx2 in Regulation of Osteoblast and Adipocyte Differentiation

Ichida

Nishimura

Hata

et al. 2004

Journal of Biological Chemistry

Self Cite

176

132

View full text Add to dashboard Cite

show abstract

“…The literature provides evidence to suggest that our findings are not the result of statistical anomaly. BMPs control stem cell commitment to various lineages and in vitro studies indicate that adipocyte differentiation depends on BMP2 dosage, precursor cell type and cell stage (23,24) and the presence of other regulators such as Schnurri-2 and PPAR-g (10,25,26). The balance between osteogenic and adipogenic effects mediated by BMP2 appear to be reciprocal and influenced by ageing, such that ageing activates adipogenic and suppresses osteogenic characters in stem cells (27)(28)(29) an observation that may contribute indirectly to the explanation of our findings.…”

Section: Discussionmentioning

confidence: 99%

Variation in the bone morphogenetic protein-2 gene: effects on fat and lean body mass in young and elderly women

McGuigan

Larzenius

Callréus

et al. 2008

European Journal of Endocrinology

View full text Add to dashboard Cite

Objective: Bone morphogenetic protein-2 (BMP2) plays a critical role in osteoblastogenesis and adipogenesis from osteoprogenitor cells. The balance between osteogenic and adipogenic effects is influenced by BMP2 concentration, transcription factors and age. BMP2 single nucleotide polymorphisms (SNPs) may contribute to osteoporosis risk, but the relationship between adiposity and body composition has not been explored. We investigated the relationship between BMP2 polymorphisms and body composition in young and elderly women. Design: Population-based association study. Methods: Four BMP2 SNPs studied. Total body fat and lean mass measured by DEXA in two cohorts: 'PEAK-25' women aged 25 (G0.00) (nZ993) and osteoporosis prospective risk assessment (OPRA) women aged 75 (G0.00) years (nZ1001). Results: We found no association between BMP2 SNPs and fat or lean mass, however, we observed consistent although non-significant trends. Polymorphisms, rs235767 and Ser37Ala, exerted opposing effects on most parameters of soft tissue and bone mass in both cohorts. This relationship appeared to be age specific with large differences between alleles observed (fat mass; Ser37Ala: 14.3% (PEAK-25), K3.5% (OPRA)). These initial results appear to suggest that alleles exerting a beneficial effect in young women may subsequently contribute to phenotypes associated with osteoporosis risk in elderly women. Conclusions: While further analyses in other comparative populations are necessary, in this study of almost 2000 women we observed interesting, although non-significant trends, regarding the effects of variation in the BMP2 gene on parameters of body mass. Although the exact nature of the relationship remains uncertain, we suggest that the mechanisms are influenced by age and environmental factors.European Journal of Endocrinology 158 661-668

show abstract

Distinct roles of BMP receptors Type IA and IB in osteo‐/chondrogenic differentiation in mesenchymal progenitors (C3H10T1/2)

et al. 2004

View full text Add to dashboard Cite

The functional roles of BMP type IA and IB receptors mediating differentiation into the osteogenic and chondrogenic lineage were investigated in the mesenchymal progenitor line C3H10T1/2 in vitro. The capacity of type IA and IB BMP receptors was assessed by the forced expression of the wild-type (wtBMPR-IA or IB) and of the kinase-deficient, dominant-negative form (dnBMPR-IA or -IB) in parental C3H10T1/2 progenitors as well as in C3H10T1/2 progenitors which recombinantly express BMP2 (C3H10T1/2-BMP2) or GDF5 (C3H10T1/2-GDF5). Consistent with the higher endogenous expression rate of BMPR-IA in comparison with BMPR-IB, BMPR-IA plays the dominant role in BMP2-mediated osteo-/chondrogenic development. BMPR-IB moderately influences osteogenic and hardly chondrogenic development. BMPR-IB seems to be unable to efficiently activate downstream signaling pathways upon forced expression. However, a mutation conferring constitutive activity to the BMPR-IB receptor indicates that this receptor possesses the capacity to activate downstream signaling cascades. These results suggest that in mesenchymal progenitors C3H10T1/2 BMPR-IA is responsible for the initiation of the osteogenic as well as chondrogenic development and that BMPR-IA and -IB receptor pathways are well separated in this mesenchymal progenitor line and may not substitute each other. In addition this indicates that type IB and IA BMP receptors may transmit different signals during the specification and differentiation of mesenchymal lineages.

show abstract

Differential Roles of Smad1 and p38 Kinase in Regulation of Peroxisome Proliferator-activating Receptor γ during Bone Morphogenetic Protein 2-induced Adipogenesis

Cited by 176 publications

References 44 publications

Reciprocal Roles of Msx2 in Regulation of Osteoblast and Adipocyte Differentiation

Reciprocal Roles of Msx2 in Regulation of Osteoblast and Adipocyte Differentiation

Variation in the bone morphogenetic protein-2 gene: effects on fat and lean body mass in young and elderly women

Distinct roles of BMP receptors Type IA and IB in osteo‐/chondrogenic differentiation in mesenchymal progenitors (C3H10T1/2)

Contact Info

Product

Resources

About