ArticleThe Journal of clinical investigation2010
The p38 MAPK pathway is essential for skeletogenesis and bone homeostasis in mice.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 231 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
231 citing papers in PubMed, 1 synthesis or guideline pooled it, 403 citations in OpenAlex.
- Beyond the Kidney: A Systematic Review of Extrarenal Manifestations inInternational journal of molecular sciences · 2026Pooled it
- Reprogramming bone homeostasis: The recoupling-oriented framework of bidirectional regulation strategies for osteoporosis.iScience · 2026Review
- Targetome-defined miR-181c signaling from extracellular vesicles governs periodontal MSC fate via RNF150-MAP3K5.Cell communication and signaling : CCS · 2026Article
- Targeting cellular senescence mitigates chemotherapy-induced bone loss in young and aged mice.GeroScience · 2026Article
- Tendon stem/progenitor cells in heterotopic ossification: functional regulation, molecular mechanisms and targeted therapeutic strategies.Journal of orthopaedic translation · 2026Review
- [Research progress on the role and mechanism of magnesium element and magnesium materials in tendon-bone interface healing].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2026Review
- High Phosphate and Low Protein Mediate Arterial and Cutaneous Vascular Calcification in CKD Mice.Journal of the American Society of Nephrology : JASN · 2026Article
- In Vitro Assessment of Osteogenic Modulation and Molecular Responses Induced by Contemporary Endodontic Sealers in MC3T3-E1 Pre-Osteoblasts.Dentistry journal · 2026Article
- TGF-β/BMP signaling in skeletal biology: molecular mechanisms, regulatory networks, and therapeutic implications in development, regeneration, and disease.Bone research · 2026Review
- Mediating Role of Muscle Mass in the Relationship Between Physical Activity and Bone Mass in Female University Students in China.PPAR research · 2026Article
- Multi-system Mechanisms in the Anti-osteoporotic Effects of Herbal Natural Products.Endocrine, metabolic & immune disorders drug targets · 2026Review
- P38α MAPK-induced senescence in cranial suture progenitor cells promotes craniosynostosis.Communications biology · 2025Article
- Gnetofuran A Enhances Osteoblast Differentiation through the p38 Signaling Pathway.Biomolecules & therapeutics · 2025Article
- Article
- Hyaluronic acid promotes biomineralization of osteoblast-like cells - observations on two different barrier membranes.International journal of implant dentistry · 2025Article
- Antioxidative fullerol prevents bone loss due to its anti-osteoclastogenic and pro-osteogenic activities.Nanomedicine : nanotechnology, biology, and medicine · 2025Article
- BMP-2-Driven Osteogenesis: A Comparative Analysis of Porcine BMSCs and ASCs and the Role of TGF-β and FGF Signaling.Biology · 2025Article
- The Role of G Protein-Coupled Receptors in the Regulation of Orthopaedic Diseases by Gut Microbiota.Nutrients · 2025Review
- Nf2-FAK signaling axis is critical for cranial bone ossification and regeneration.Nature communications · 2025Article
- O-GlcNAcylation: Sagacious Orchestrator of Bone-, Joint-, and Spine-Related Diseases.Journal of proteome research · 2025Review
171 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
Abstract
Nearly every extracellular ligand that has been found to play a role in regulating bone biology acts, at least in part, through MAPK pathways. Nevertheless, much remains to be learned about the contribution of MAPKs to osteoblast biology in vivo. Here we report that the p38 MAPK pathway is required for normal skeletogenesis in mice, as mice with deletion of any of the MAPK pathway member-encoding genes MAPK kinase 3 (Mkk3), Mkk6, p38a, or p38b displayed profoundly reduced bone mass secondary to defective osteoblast differentiation. Among the MAPK kinase kinase (MAP3K) family, we identified TGF-beta-activated kinase 1 (TAK1; also known as MAP3K7) as the critical activator upstream of p38 in osteoblasts. Osteoblast-specific deletion of Tak1 resulted in clavicular hypoplasia and delayed fontanelle fusion, a phenotype similar to the cleidocranial dysplasia observed in humans haploinsufficient for the transcription factor runt-related transcription factor 2 (Runx2). Mechanistic analysis revealed that the TAK1-MKK3/6-p38 MAPK axis phosphorylated Runx2, promoting its association with the coactivator CREB-binding protein (CBP), which was required to regulate osteoblast genetic programs. These findings reveal an in vivo function for p38beta and establish that MAPK signaling is essential for bone formation in vivo. These results also suggest that selective p38beta agonists may represent attractive therapeutic agents to prevent bone loss associated with osteoporosis and aging.
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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.