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Autocrine stimulation of osteoblast activity by Wnt5a in response to TNF-α in human mesenchymal stem cells
- Source :
- Biochemical and Biophysical Research Communications, Biochemical and Biophysical Research Communications, Elsevier, 2013, 430 (3), pp.1072-7. ⟨10.1016/j.bbrc.2012.12.036⟩, Europe PubMed Central, Biochemical and Biophysical Research Communications, Vol. 430, No 3 (2013) pp. 1072-1077
- Publication Year :
- 2013
- Publisher :
- HAL CCSD, 2013.
-
Abstract
- International audience; Although anti-tumor necrosis factor (TNF)-α treatments efficiently block inflammation in ankylosing spondylitis (AS), they are inefficient to prevent excessive bone formation. In AS, ossification seems more prone to develop in sites where inflammation has resolved following anti-TNF therapy, suggesting that TNF-α indirectly stimulates ossification. In this context, our objectives were to determine and compare the involvement of Wnt proteins, which are potent growth factors of bone formation, in the effects of TNF-α on osteoblast function. In human mesenchymal stem cells (MSCs), TNF-α significantly increased the levels of Wnt10b and Wnt5a. Associated with this effect, TNF-α stimulated tissue-non specific alkaline phosphatase (TNAP) and mineralization. This effect was mimicked by activation of the canonical β-catenin pathway with either anti-Dkk1 antibodies, lithium chloride (LiCl) or SB216763. TNF-α reduced, and activation of β-catenin had little effect on expression of osteocalcin, a late marker of osteoblast differentiation. Surprisingly, TNF-α failed to stabilize β-catenin and Dkk1 did not inhibit TNF-α effects. In fact, Dkk1 expression was also enhanced in response to TNF-α, perhaps explaining why canonical signaling by Wnt10b was not activated by TNF-α. However, we found that Wnt5a also stimulated TNAP in MSCs cultured in osteogenic conditions, and increased the levels of inflammatory markers such as COX-2. Interestingly, treatment with anti-Wnt5a antibodies reduced endogenous TNAP expression and activity. Collectively, these data suggest that increased levels of Dkk1 may blunt the autocrine effects of Wnt10b, but not that of Wnt5a, acting through non-canonical signaling. Thus, Wnt5a may be potentially involved in the effects of inflammation on bone formation.
- Subjects :
- Male
Indoles
Cellular differentiation
MESH: beta Catenin
Biochemistry
Maleimides
0302 clinical medicine
MESH: Alkaline Phosphatase
Osteogenesis
MESH: Osteogenesis
Cells, Cultured
beta Catenin
MESH: Maleimides
MESH: Indoles
0303 health sciences
Osteoblast
Wnt signaling pathway
Cell Differentiation
MESH: Lithium Chloride
MESH: Spondylitis, Ankylosing
MESH: Wnt Proteins
medicine.anatomical_structure
030220 oncology & carcinogenesis
Intercellular Signaling Peptides and Proteins
Tumor necrosis factor alpha
medicine.symptom
Stem cell
TNF-alpha
Ankylosing spondylitis
MESH: Cells, Cultured
Adult
MESH: Cell Differentiation
medicine.medical_specialty
Mineralization
Biophysics
Inflammation
Biology
Wnt-5a Protein
MESH: Calcification, Physiologic
03 medical and health sciences
Wnt
Calcification, Physiologic
Internal medicine
Proto-Oncogene Proteins
Alkaline phosphatase
medicine
Humans
Spondylitis, Ankylosing
[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM]
Autocrine signalling
MESH: Intercellular Signaling Peptides and Proteins
Molecular Biology
030304 developmental biology
MESH: Osteoblasts
Osteoblasts
MESH: Humans
Tumor Necrosis Factor-alpha
Mesenchymal stem cell
Mesenchymal Stem Cells
MESH: Adult
Cell Biology
Alkaline Phosphatase
MESH: Male
Wnt Proteins
MESH: Proto-Oncogene Proteins
Endocrinology
MESH: Tumor Necrosis Factor-alpha
ddc:618.97
Cancer research
MESH: Mesenchymal Stromal Cells
Lithium Chloride
Subjects
Details
- Language :
- English
- ISSN :
- 0006291X and 10902104
- Database :
- OpenAIRE
- Journal :
- Biochemical and Biophysical Research Communications, Biochemical and Biophysical Research Communications, Elsevier, 2013, 430 (3), pp.1072-7. ⟨10.1016/j.bbrc.2012.12.036⟩, Europe PubMed Central, Biochemical and Biophysical Research Communications, Vol. 430, No 3 (2013) pp. 1072-1077
- Accession number :
- edsair.doi.dedup.....9c57f201113994fa736dbc9347dc4675