JAK/STAT as a Potential Therapeutic Target for Osteolytic Diseases
Several cytokines with major biological functions in inflammatory diseases exert their functions through the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signal transduction pathway. JAKs phosphorylate the cytoplasmic domain of the receptor, inducing the activation of i...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/12/10290 |
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| author | Mariely A. Godoi Angelo C. Camilli Karen G. A. Gonzales Vitória B. Costa Evangelos Papathanasiou Fábio R. M. Leite Morgana R. Guimarães-Stabili |
| author_facet | Mariely A. Godoi Angelo C. Camilli Karen G. A. Gonzales Vitória B. Costa Evangelos Papathanasiou Fábio R. M. Leite Morgana R. Guimarães-Stabili |
| author_sort | Mariely A. Godoi |
| collection | DOAJ |
| description | Several cytokines with major biological functions in inflammatory diseases exert their functions through the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signal transduction pathway. JAKs phosphorylate the cytoplasmic domain of the receptor, inducing the activation of its substrates, mainly the proteins known as STATs. STATs bind to these phosphorylated tyrosine residues and translocate from the cytoplasm to the nucleus, further regulating the transcription of several genes that regulate the inflammatory response. The JAK/STAT signaling pathway plays a critical role in the pathogenesis of inflammatory diseases. There is also increasing evidence indicating that the persistent activation of the JAK/STAT signaling pathway is related to several inflammatory bone (osteolytic) diseases. However, the specific mechanism remains to be clarified. JAK/STAT signaling pathway inhibitors have gained major scientific interest to explore their potential in the prevention of the destruction of mineralized tissues in osteolytic diseases. Here, our review highlights the importance of the JAK/STAT signaling pathway in inflammation-induced bone resorption and presents the results of clinical studies and experimental models of JAK inhibitors in osteolytic diseases. |
| first_indexed | 2024-03-11T02:20:43Z |
| format | Article |
| id | doaj.art-c6feb84337ef42879e1166d70faf2394 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T02:20:43Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c6feb84337ef42879e1166d70faf23942023-11-18T10:51:26ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-0124121029010.3390/ijms241210290JAK/STAT as a Potential Therapeutic Target for Osteolytic DiseasesMariely A. Godoi0Angelo C. Camilli1Karen G. A. Gonzales2Vitória B. Costa3Evangelos Papathanasiou4Fábio R. M. Leite5Morgana R. Guimarães-Stabili6Department of Diagnosis and Surgery, School of Dentistry at Araraquara, UNESP, Araraquara 14801-385, BrazilDepartment of Diagnosis and Surgery, School of Dentistry at Araraquara, UNESP, Araraquara 14801-385, BrazilDepartment of Diagnosis and Surgery, School of Dentistry at Araraquara, UNESP, Araraquara 14801-385, BrazilDepartment of Diagnosis and Surgery, School of Dentistry at Araraquara, UNESP, Araraquara 14801-385, BrazilDepartment of Periodontology, Tufts University School of Dental Medicine, Boston, MA 02111, USANational Dental Research Institute Singapore, National Dental Centre, Singapore 168938, SingaporeDepartment of Diagnosis and Surgery, School of Dentistry at Araraquara, UNESP, Araraquara 14801-385, BrazilSeveral cytokines with major biological functions in inflammatory diseases exert their functions through the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signal transduction pathway. JAKs phosphorylate the cytoplasmic domain of the receptor, inducing the activation of its substrates, mainly the proteins known as STATs. STATs bind to these phosphorylated tyrosine residues and translocate from the cytoplasm to the nucleus, further regulating the transcription of several genes that regulate the inflammatory response. The JAK/STAT signaling pathway plays a critical role in the pathogenesis of inflammatory diseases. There is also increasing evidence indicating that the persistent activation of the JAK/STAT signaling pathway is related to several inflammatory bone (osteolytic) diseases. However, the specific mechanism remains to be clarified. JAK/STAT signaling pathway inhibitors have gained major scientific interest to explore their potential in the prevention of the destruction of mineralized tissues in osteolytic diseases. Here, our review highlights the importance of the JAK/STAT signaling pathway in inflammation-induced bone resorption and presents the results of clinical studies and experimental models of JAK inhibitors in osteolytic diseases.https://www.mdpi.com/1422-0067/24/12/10290JAK/STAT inhibitorosteoclastsosteoblastscytokinesJAK/STAT signaling pathwayosteolysis |
| spellingShingle | Mariely A. Godoi Angelo C. Camilli Karen G. A. Gonzales Vitória B. Costa Evangelos Papathanasiou Fábio R. M. Leite Morgana R. Guimarães-Stabili JAK/STAT as a Potential Therapeutic Target for Osteolytic Diseases International Journal of Molecular Sciences JAK/STAT inhibitor osteoclasts osteoblasts cytokines JAK/STAT signaling pathway osteolysis |
| title | JAK/STAT as a Potential Therapeutic Target for Osteolytic Diseases |
| title_full | JAK/STAT as a Potential Therapeutic Target for Osteolytic Diseases |
| title_fullStr | JAK/STAT as a Potential Therapeutic Target for Osteolytic Diseases |
| title_full_unstemmed | JAK/STAT as a Potential Therapeutic Target for Osteolytic Diseases |
| title_short | JAK/STAT as a Potential Therapeutic Target for Osteolytic Diseases |
| title_sort | jak stat as a potential therapeutic target for osteolytic diseases |
| topic | JAK/STAT inhibitor osteoclasts osteoblasts cytokines JAK/STAT signaling pathway osteolysis |
| url | https://www.mdpi.com/1422-0067/24/12/10290 |
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