ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2016
Osteoclast TGF-β Receptor Signaling Induces Wnt1 Secretion and Couples Bone Resorption to Bone Formation.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 85 citations in OpenAlex.
- Periodontitis as a Model for Inflammatory Uncoupling of Bone Remodeling.Journal of periodontal research · 2026Review
- TGF-β/BMP signaling in skeletal biology: molecular mechanisms, regulatory networks, and therapeutic implications in development, regeneration, and disease.Bone research · 2026Review
- Direct and indirect effects of transforming growth factor-beta on osteoclast-mediated bone remodeling using a new in vitro bone matrix model.JBMR plus · 2025Article
- Signaling Dynamics in Osteogenesis: Unraveling Therapeutic Targets for Bone Generation.Current drug targets · 2025Review
- Aging impairs the osteocytic regulation of collagen integrity and bone quality.Bone research · 2024Article
- Rc3h1 negatively regulates osteoclastogenesis by limiting energy metabolism.Theranostics · 2024Article
- TGF-β signaling in the cranial neural crest affects late-stage mandibular bone resorption and length.Frontiers in physiology · 2024Article
- Traditional Chinese medicine in osteoporosis: from pathogenesis to potential activity.Frontiers in pharmacology · 2024Review
- Article
- Atp6i deficient mouse model uncovers transforming growth factor-β1 /Smad2/3 as a key signaling pathway regulating odontoblast differentiation and tooth root formation.International journal of oral science · 2023Article
- The Multifaceted Effects of Osteocytic TGFβ Signaling on the Skeletal and Extraskeletal Functions of Bone.Current osteoporosis reports · 2023Review
- IRAK4 inhibition: an effective strategy for immunomodulating peri-implant osseointegration via reciprocally-shifted polarization in the monocyte-macrophage lineage cells.BMC oral health · 2023Article
- Research Advances on Stem Cell-Derived Extracellular Vesicles Promoting the Reconstruction of Alveolar Bone through RANKL/RANK/OPG Pathway.Journal of functional biomaterials · 2023Review
- Low energy availability reduces bone mass and gonadal function in male mice.Journal of bone and mineral metabolism · 2023Article
- Intra-pituitary follicle-stimulating hormone signaling regulates hepatic lipid metabolism in mice.Nature communications · 2023Article
- Article
- Trabecular bone remodeling in the aging mouse: A micro-multiphysics agent-basedFrontiers in bioengineering and biotechnology · 2023Article
- Bioactivation of 3D Cell-Imprinted Polydimethylsiloxane Surfaces by Bone Protein Nanocoating for Bone Tissue Engineering.ACS omega · 2022Article
- Bone remodeling: an operational process ensuring survival and bone mechanical competence.Bone research · 2022Review
- Connection between Mesenchymal Stem Cells Therapy and Osteoclasts in Osteoarthritis.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Osteoblast-mediated bone formation is coupled to osteoclast-mediated bone resorption. These processes become uncoupled with age, leading to increased risk for debilitating fractures. Therefore, understanding how osteoblasts are recruited to sites of resorption is vital to treating age-related bone loss. Osteoclasts release and activate TGF-β from the bone matrix. Here we show that osteoclast-specific inhibition of TGF-β receptor signaling in mice results in osteopenia due to reduced osteoblast numbers with no significant impact on osteoclast numbers or activity. TGF-β induced osteoclast expression of Wnt1, a protein crucial to normal bone formation, and this response was blocked by impaired TGF-β receptor signaling. Osteoclasts in aged murine bones had lower TGF-β signaling and Wnt1 expression in vivo. Ex vivo stimulation of osteoclasts derived from young or old mouse bone marrow macrophages showed no difference in TGF-β-induced Wnt1 expression. However, young osteoclasts expressed reduced Wnt1 when cultured on aged mouse bone chips compared to young mouse bone chips, consistent with decreased skeletal TGF-β availability with age. Therefore, osteoclast responses to TGF-β are essential for coupling bone resorption to bone formation, and modulating this pathway may provide opportunities to treat age-related bone loss.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.