Reciprocal Roles of Msx2 in Regulation of Osteoblast and Adipocyte Differentiation
Open accessAbstract
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 observed in mesenchymal cells isolated from Runx2-deficient mice. Interestingly the expression of Msx2 was induced by bone morphogenetic protein 2 treatment in Runx2-deficient mesenchymal cells. In contrast, Msx2 diminished peroxisome proliferator-activated receptor gamma (PPARgamma) expression and adipogenesis of the preadipocytic cell line 3T3-F442A. Moreover Msx2 inhibited the transcriptional activity of PPARgamma, CCAAT/enhancer-binding protein beta (C/EBPbeta), and C/EBPdelta and blocked adipocyte differentiation of mesenchymal cells induced by overexpression of PPARgamma, C/EBPalpha, C/EBPbeta, or C/EBPdelta. These data indicate that Msx2 promotes osteoblast differentiation independently of Runx2 and negatively regulates adipocyte differentiation through inhibition of PPARgamma and the C/EBP family.
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Msx2 promotes primary murine osteoblast differentiation and calcification in concert with typical osteoblastic transcription factors, and ectopic Msx2 rescues impaired osteoblastogenesis induced by Runx2 deficiency.
“It has been reported that Msx2 promotes primary murine osteoblast differentiation and calcification in concert with typical osteoblastic transcription factors, and ectopic Msx2 rescues the impaired osteoblastogenesis induced by Runx2 deficiency47,48.”
From Targeting Msx2 as a brake in the fusion fate of osteoclasts and an anabolic therapy in pre-clinical models of osteoporosis (2025) · cites this paper as [48]
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- Authors
- Ichida, F., Nishimura, R., Hata, K., Matsubara, T., Ikeda, F., Hisada, K., Yatani, H., Cao, X., Komori, T., Yamaguchi, A., & Yoneda, T.
- Affiliations
- The University of Osaka (JP)
- University of Alabama at Birmingham (US)
- Nagasaki University (JP)
- Corresponding author
- Nishimura, Riko
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2004-08
- Volume
- 279
- Issue
- 32
- Pages
- 34015-34022
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2159856988
- Semantic Scholar
- 38d97e6b74a3110b2c0d5a8840949de55e4196d7
- Cited by
- 173
- References
- 33
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 5 · 2020: 7 · 2019: 4 · 2018: 2 · 2017: 1 · 2016: 5 · 2015: 10 · 2014: 7 · 2013: 15 · 2012: 17
- FWCI
- 4.38
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- Msx2, osteogenic differentiation, adipogenesis, bone formation, Runx2, PPARγ, C/EBP transcription factors, BMP-2, mesenchymal cells, alkaline phosphatase, 3T3-F442A cells, C2C12 myoblasts, C3H10T1/2 cells, C/EBPα
- MeSH terms
- Alkaline Phosphatase, Animals, Cell Differentiation, Cell Line, DNA-Binding Proteins, Cricetinae, Mesoderm, Mice, Inbred C3H, Neoplasm Proteins, Osteoblasts, Recombinant Proteins, Stem Cells, Transcription Factors, Transfection, Gene Expression, Transforming Growth Factor beta, CHO Cells, Adipocytes, Receptors, Cytoplasmic and Nuclear, Homeodomain Proteins, Bone Morphogenetic Proteins, Reverse Transcriptase Polymerase Chain Reaction, CCAAT-Enhancer-Binding Protein-alpha, CCAAT-Enhancer-Binding Protein-beta, Core Binding Factor Alpha 1 Subunit, Mice, Bone Morphogenetic Protein 2
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