PTPN11 in cartilage development, adult homeostasis, and diseases
Abstract The SH2 domain-containing protein tyrosine phosphatase 2 (SHP2, also known as PTP2C), encoded by PTPN11, is ubiquitously expressed and has context-specific effects. It promotes RAS/MAPK signaling downstream of receptor tyrosine kinases, cytokine receptors, and extracellular matrix proteins,...
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| Format: | Article |
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Nature Publishing Group
2025-05-01
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| Series: | Bone Research |
| Online Access: | https://doi.org/10.1038/s41413-025-00425-0 |
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| author | Wentian Yang Véronique Lefebvre |
| author_facet | Wentian Yang Véronique Lefebvre |
| author_sort | Wentian Yang |
| collection | DOAJ |
| description | Abstract The SH2 domain-containing protein tyrosine phosphatase 2 (SHP2, also known as PTP2C), encoded by PTPN11, is ubiquitously expressed and has context-specific effects. It promotes RAS/MAPK signaling downstream of receptor tyrosine kinases, cytokine receptors, and extracellular matrix proteins, and was shown in various lineages to modulate cell survival, proliferation, differentiation, and migration. Over the past decade, PTPN11 inactivation in chondrocytes was found to cause metachondromatosis, a rare disorder characterized by multiple enchondromas and osteochondroma-like lesions. Moreover, SHP2 inhibition was found to mitigate osteoarthritis pathogenesis in mice, and abundant but incomplete evidence suggests that SHP2 is crucial for cartilage development and adult homeostasis, during which its expression and activity are tightly regulated transcriptionally and posttranslationally, and by varying sets of functional partners. Fully uncovering SHP2 actions and regulation in chondrocytes is thus fundamental to understanding the mechanisms underlying both rare and common cartilage diseases and to designing effective disease treatments. We here review current knowledge, highlight recent discoveries and controversies, and propose new research directions to answer remaining questions. |
| format | Article |
| id | doaj-art-fd597872436c4a1596bf2d1c6aacbf3f |
| institution | OA Journals |
| issn | 2095-6231 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Bone Research |
| spelling | doaj-art-fd597872436c4a1596bf2d1c6aacbf3f2025-08-20T01:51:31ZengNature Publishing GroupBone Research2095-62312025-05-0113111510.1038/s41413-025-00425-0PTPN11 in cartilage development, adult homeostasis, and diseasesWentian Yang0Véronique Lefebvre1Department of Orthopaedic Surgery, Brown University Alpert Medical School and Rhode Island HospitalDivision of Orthopaedic Surgery, Department of Surgery, Children’s Hospital of PhiladelphiaAbstract The SH2 domain-containing protein tyrosine phosphatase 2 (SHP2, also known as PTP2C), encoded by PTPN11, is ubiquitously expressed and has context-specific effects. It promotes RAS/MAPK signaling downstream of receptor tyrosine kinases, cytokine receptors, and extracellular matrix proteins, and was shown in various lineages to modulate cell survival, proliferation, differentiation, and migration. Over the past decade, PTPN11 inactivation in chondrocytes was found to cause metachondromatosis, a rare disorder characterized by multiple enchondromas and osteochondroma-like lesions. Moreover, SHP2 inhibition was found to mitigate osteoarthritis pathogenesis in mice, and abundant but incomplete evidence suggests that SHP2 is crucial for cartilage development and adult homeostasis, during which its expression and activity are tightly regulated transcriptionally and posttranslationally, and by varying sets of functional partners. Fully uncovering SHP2 actions and regulation in chondrocytes is thus fundamental to understanding the mechanisms underlying both rare and common cartilage diseases and to designing effective disease treatments. We here review current knowledge, highlight recent discoveries and controversies, and propose new research directions to answer remaining questions.https://doi.org/10.1038/s41413-025-00425-0 |
| spellingShingle | Wentian Yang Véronique Lefebvre PTPN11 in cartilage development, adult homeostasis, and diseases Bone Research |
| title | PTPN11 in cartilage development, adult homeostasis, and diseases |
| title_full | PTPN11 in cartilage development, adult homeostasis, and diseases |
| title_fullStr | PTPN11 in cartilage development, adult homeostasis, and diseases |
| title_full_unstemmed | PTPN11 in cartilage development, adult homeostasis, and diseases |
| title_short | PTPN11 in cartilage development, adult homeostasis, and diseases |
| title_sort | ptpn11 in cartilage development adult homeostasis and diseases |
| url | https://doi.org/10.1038/s41413-025-00425-0 |
| work_keys_str_mv | AT wentianyang ptpn11incartilagedevelopmentadulthomeostasisanddiseases AT veroniquelefebvre ptpn11incartilagedevelopmentadulthomeostasisanddiseases |