ArticleThe Journal of clinical investigation2004
Glycoprotein 130 regulates bone turnover and bone size by distinct downstream signaling pathways.
Article in The Journal of clinical investigation, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 193 citations in OpenAlex.
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- Osteogenic Differentiation Induced by Dental Pulp Stem Cells Secretome: A Dose-Dependent Comparative Study.Clinical and experimental dental research · 2026Article
- Role of Cytokines in Bone Diseases and Their Therapeutic Application.ImmunoTargets and therapy · 2026Review
- IL6ST participates in the development of adolescent idiopathic scoliosis by regulating bone marrow mesenchymal stem cells.Communications biology · 2025Article
- Are Dietary Habits the Missing Link Between Hashimoto's Thyroiditis and Osteoporosis?Nutrients · 2025Review
- Roles of myokines in osteoporosis under physiological and diabetic conditions.Frontiers in endocrinology · 2025Review
- Osteoclast-derived coupling factors: origins and state-of-play Louis V Avioli lecture, ASBMR 2023.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024Article
- Preclinical Rodent Models for Human Bone Disease, Including a Focus on Cortical Bone.Endocrine reviews · 2024Review
- Advanced Ti-Nb-Ta Alloys for Bone Implants with Improved Functionality.Journal of functional biomaterials · 2024Article
- From Stem to Sternum: The Role of Shp2 in the Skeleton.Calcified tissue international · 2023Review
- How does Hashimoto's thyroiditis affect bone metabolism?Reviews in endocrine & metabolic disorders · 2023Review
- The Cell-Specific Role of SHP2 in Regulating Bone Homeostasis and Regeneration Niches.International journal of molecular sciences · 2023Review
- Effects of the Interleukin-6 Receptor Blocker Sarilumab on Metabolic Activity and Differentiation Capacity of Primary Human Osteoblasts.Pharmaceutics · 2022Article
- The role of IL-6 and osteoprotegerin in bone metabolism in patients with Graves' disease.Turkish journal of medical sciences · 2022Article
- Stimulation of Osteoclast Formation by Oncostatin M and the Role of WNT16 as a Negative Feedback Regulator.International journal of molecular sciences · 2022Review
- Protein tyrosine phosphatases in skeletal development and diseases.Bone research · 2022Review
- gp130/STAT3 signaling is required for homeostatic proliferation and anabolism in postnatal growth plate and articular chondrocytes.Communications biology · 2022Article
- STAT3 Signalling via the IL-6ST/gp130 Cytokine Receptor Promotes Epithelial Integrity and Intestinal Barrier Function during DSS-Induced Colitis.Biomedicines · 2021Article
- Review
- Emerging insights into the comparative effectiveness of anabolic therapies for osteoporosis.Nature reviews. Endocrinology · 2021Review
3 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
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The gp130-dependent cytokines, which signal through at least two intracellular pathways, regulate osteoclast and osteoblast formation. To define their roles in regulating bone mass, we analyzed mice in which gp130 signaling via either the signal transducer and activator of transcription (STAT) 1/3 (gp130(DeltaSTAT/DeltaSTAT)) or SHP2/ras/MAPK (gp130(Y757F/Y757F)) pathway was attenuated. In gp130(DeltaSTAT/DeltaSTAT) mice, trabecular bone volume (BV/TV) and turnover were normal, but bone length was reduced by premature growth plate closure, indicating an essential role for gp130-STAT1/3 signaling in chondrocyte differentiation. In contrast, while bone size was normal in gp130(Y757F/Y757F) mice, BV/TV was reduced due to high bone turnover, indicated by high osteoclast surface/bone surface (OcS/BS) and osteoblast surface/bone surface (ObS/BS). Furthermore, generation of functional osteoclasts from bone marrow of gp130(Y757F/Y757F) mice was elevated, revealing that while gp130 family cytokines stimulate osteoclastogenesis through the osteoblast lineage, gp130, via SHP2/Ras/MAPK, inhibits osteoclastogenesis in a cell lineage-autonomous manner. Genetic ablation of IL-6 in gp130(Y757F/Y757F) mice exacerbated this osteopenia by reducing ObS/BS without affecting OcS/BS. Thus, while IL-6 is critical for high bone formation in gp130(Y757F/Y757F) mice, it is not involved in the increased osteoclastogenesis. In conclusion, gp130 is essential for normal bone growth and trabecular bone mass, with balanced regulation depending on selective activation of STAT1/3 and SHP2/ras/MAPK, respectively. Furthermore, the latter pathway can directly inhibit osteoclastogenesis in vivo.
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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.