Sequential roles of Hedgehog and Wnt signaling in osteoblast development
Abstract
Signals that govern development of the osteoblast lineage are not well understood. Indian hedgehog (Ihh), a member of the hedgehog (Hh) family of proteins, is essential for osteogenesis in the endochondral skeleton during embryogenesis. The canonical pathway of Wnt signaling has been implicated by studies of Lrp5, a co-receptor for Wnt proteins, in postnatal bone mass homeostasis. In the present study we demonstrate that β-catenin, a central player in the canonical Wnt pathway, is indispensable for osteoblast differentiation in the mouse embryo. Moreover, we present evidence that Wnt signaling functions downstream of Ihh in development of the osteoblast lineage. Finally Wnt7b is identified as a potential endogenous ligand regulating osteogenesis. These data support a model that integrates Hh and Wnt signaling in the regulation of osteoblast development.
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β-catenin is required for bone formation and is activated during multiple stages of osteoblast differentiation to regulate both osteoblast and osteoclast.
“Many studies have demonstrated that β-catenin is required for bone formation and is activated during multiple stages of osteoblast differentiation to regulate both osteoblast and osteoclast.40–43”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [41]
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- Authors
- Hu, H., Hilton, M. J., Tu, X., Yu, K., Ornitz, D. M., & Long, F.
- Affiliations
- Washington University in St. Louis (US)
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2005-01-01
- Volume
- 132
- Issue
- 1
- Pages
- 49-60
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W1999322873
- Cited by
- 682
- References
- 56
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 19 · 2023: 10 · 2022: 18 · 2021: 22 · 2020: 29 · 2019: 31 · 2018: 32 · 2017: 33 · 2016: 25 · 2015: 35 · 2014: 48 · 2013: 44 · 2012: 41
- FWCI
- 12.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Development (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK065789, R01DK065789)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (5 T32 AR07033, T32AR007033)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD39952, P01HD039952)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
- Keywords
- Hedgehog signaling, Wnt signaling, osteogenic differentiation, Indian hedgehog, β-catenin, Wnt7b, bone formation, embryonic bone development, LRP5, Wnt co-receptor, bone homeostasis
- MeSH terms
- Animals, Cell Differentiation, Cytoskeletal Proteins, Embryo, Mammalian, Glycoproteins, Ligands, Mice, Inbred C3H, Osteoblasts, Proto-Oncogene Proteins, Receptors, LDL, Retroviridae, Time Factors, Signal Transduction, Trans-Activators, Gene Expression Regulation, Developmental, Cell Lineage, Chondrocytes, Reverse Transcriptase Polymerase Chain Reaction, LDL-Receptor Related Proteins, Intercellular Signaling Peptides and Proteins, Cell Proliferation, Wnt Proteins, beta Catenin, Mice, Hedgehog Proteins, Low Density Lipoprotein Receptor-Related Protein-5
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