ArticleDisease models & mechanisms2011
Development of severe skeletal defects in induced SHP-2-deficient adult mice: a model of skeletal malformation in humans with SHP-2 mutations.
Article in Disease models & mechanisms, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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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.
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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
28 citing papers in PubMed, 53 citations in OpenAlex.
- SOS1 inhibition suppresses the emergence of osimertinib resistance to generate a durable response inScience signaling · 2025Article
- PTPN11 in cartilage development, adult homeostasis, and diseases.Bone research · 2025Review
- SHP2 inhibition by SHP099 attenuates IL-6-driven osteoclastogenesis in growth plate injury.Frontiers in immunology · 2025Article
- SLAMF8 regulates osteogenesis and adipogenesis of bone marrow mesenchymal stem cells via S100A6/Wnt/β-catenin signaling pathway.Stem cell research & therapy · 2024Article
- Article
- Osteoclast Methods in Protein Phosphatase Research.Methods in molecular biology (Clifton, N.J.) · 2024Article
- From Stem to Sternum: The Role of Shp2 in the Skeleton.Calcified tissue international · 2023Review
- The Cell-Specific Role of SHP2 in Regulating Bone Homeostasis and Regeneration Niches.International journal of molecular sciences · 2023Review
- Skeletal defects and bone metabolism in Noonan, Costello and cardio-facio-cutaneous syndromes.Frontiers in endocrinology · 2023Review
- Growth, Endocrine Features, and Growth Hormone Treatment in Noonan Syndrome.Journal of clinical medicine · 2022Review
- Endocrine system involvement in patients with RASopathies: A case series.Frontiers in endocrinology · 2022Article
- Effect of environmental tobacco smoke on COX-2 and SHP-2 expression in a periodontitis rat model.Oral diseases · 2021Article
- Etiology and Treatment of Growth Delay in Noonan Syndrome.Frontiers in endocrinology · 2021Review
- Noonan syndrome-causing SHP2 mutants impair ERK-dependent chondrocyte differentiation during endochondral bone growth.Human molecular genetics · 2018Article
- Article
- Identification of novel genetic loci for osteoporosis and/or rheumatoid arthritis using cFDR approach.PloS one · 2017Article
- AbnormalJCI insight · 2016Article
- FGFR3 Deficiency Causes Multiple Chondroma-like Lesions by Upregulating Hedgehog Signaling.PLoS genetics · 2015Article
- SHP2 regulates osteoclastogenesis by promoting preosteoclast fusion.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015Article
- Protein tyrosine phosphatases ε and α perform nonredundant roles in osteoclasts.Molecular biology of the cell · 2014Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
SHP-2 (encoded by PTPN11) is a ubiquitously expressed protein tyrosine phosphatase required for signal transduction by multiple different cell surface receptors. Humans with germline SHP-2 mutations develop Noonan syndrome or LEOPARD syndrome, which are characterized by cardiovascular, neurological and skeletal abnormalities. To study how SHP-2 regulates tissue homeostasis in normal adults, we used a conditional SHP-2 mouse mutant in which loss of expression of SHP-2 was induced in multiple tissues in response to drug administration. Induced deletion of SHP-2 resulted in impaired hematopoiesis, weight loss and lethality. Most strikingly, induced SHP-2-deficient mice developed severe skeletal abnormalities, including kyphoses and scolioses of the spine. Skeletal malformations were associated with alterations in cartilage and a marked increase in trabecular bone mass. Osteoclasts were essentially absent from the bones of SHP-2-deficient mice, thus accounting for the osteopetrotic phenotype. Studies in vitro revealed that osteoclastogenesis that was stimulated by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa B ligand (RANKL) was defective in SHP-2-deficient mice. At least in part, this was explained by a requirement for SHP-2 in M-CSF-induced activation of the pro-survival protein kinase AKT in hematopoietic precursor cells. These findings illustrate an essential role for SHP-2 in skeletal growth and remodeling in adults, and reveal some of the cellular and molecular mechanisms involved. The model is predicted to be of further use in understanding how SHP-2 regulates skeletal morphogenesis, which could lead to the development of novel therapies for the treatment of skeletal malformations in human patients with SHP-2 mutations.
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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.