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Activation of the JAK-STAT signal transduction pathway by oncostatin-M cultured human and mouse osteoblastic cells
1Department of Orthopaedics, Yale University School of Medicine, New Haven, Connecticut 06520-8071, USA.
Abstract:
Oncastatin M (OSM) is one member of the leukemia inhibitory factor/interleukin-6 family of cytokines that has been shown to be a growth regulatory molecule. In osteoblastic cultures, OSM causes marked phenotypic changes and the enhanced secretion of interleukin-6. In this study, we have shown that stimulation of murine and human osteoblastic cultures and a human osteosarcoma cell line with OSM resulted in the tyrosine phosphorylation of a number of cellular proteins including members of both the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) family of signaling proteins. The JAKs, a family of intracellular kinases, and the STATs, a family of transcription factors, have both previously been shown to be tyrosine phosphorylated and activated in response to various cytokines, interferons, and growth factors in cells of non-skeletal origin. Using three different sources of cells of the osteoblast lineage, we demonstrate that OSM induces a rapid but transient tyrosine phosphorylation of the three JAK family members tested, JAK1, JAK2 and Tyk2. In addition, two members of the STAT family, Stat1alpha and Stat3, are tyrosine phosphorylated in osteoblastic cells in culture in response to OSM. OSM activation of this pathway in cells of the osteoblast lineage will result in the transcription of specific genes that ultimately may be associated with osteoblast function.
Insights
Oncastatin M (OSM) activates Janus kinase (JAK) and signal transducer and activator of transcription (STAT) proteins in osteoblast cells. This signaling pathway influences gene transcription related to osteoblast function.
Area of Science:
- Cellular and Molecular Biology
- Bone Biology and Metabolism
- Signal Transduction
Background:
- Oncastatin M (OSM) is a cytokine in the leukemia inhibitory factor/interleukin-6 family.
- OSM acts as a growth regulatory molecule and influences osteoblastic cultures.
- OSM induces phenotypic changes and interleukin-6 secretion in osteoblasts.
Purpose of the Study:
- To investigate the effects of OSM on intracellular signaling pathways in osteoblast lineage cells.
- To determine if OSM activates Janus kinase (JAK) and signal transducer and activator of transcription (STAT) proteins in these cells.
- To elucidate the role of OSM-induced signaling in osteoblast function.
Main Methods:
- Stimulation of murine and human osteoblastic cultures and a human osteosarcoma cell line with OSM.
- Analysis of tyrosine phosphorylation of cellular proteins, including JAK and STAT family members.
- Utilized three different sources of osteoblast lineage cells.
Main Results:
- OSM stimulation resulted in tyrosine phosphorylation of multiple cellular proteins.
- OSM rapidly and transiently induced tyrosine phosphorylation of JAK1, JAK2, and Tyk2.
- OSM also caused tyrosine phosphorylation of Stat1alpha and Stat3 in osteoblastic cells.
Conclusions:
- OSM activates the JAK/STAT signaling pathway in cells of the osteoblast lineage.
- This activation leads to the transcription of specific genes.
- The OSM-induced signaling pathway is potentially associated with osteoblast function and regulation.