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JNK1 modulates osteoclastogenesis through both c-Jun phosphorylation-dependent and -independent mechanisms
Jean-Pierre David1, Kanaga Sabapathy, Oskar Hoffmann
1Research Institute of Molecular Pathology, Dr Bohr-Gasse 7, A-1030 Vienna, Austria.
Journal of Cell Science
|October 12, 2002
Summary
Jun kinases (JNKs) play a crucial role in bone cell differentiation. JNK1 activation by RANKL is essential for osteoclastogenesis, impacting both cell survival and transcription factor activity.
Area of Science:
- Cell Biology
- Molecular Biology
- Immunology
Background:
- Jun kinases (JNKs) modulate the transcription factor AP-1 activity through c-Jun phosphorylation.
- c-Fos is essential for osteoclast differentiation, and AP-1 activity is critical for this process.
Purpose of the Study:
- To investigate the specific roles of JNK1 and JNK2 in osteoclast differentiation.
- To determine the mechanisms by which JNK1 influences osteoclastogenesis.
Main Methods:
- Utilized knockout mice lacking JNK1 or JNK2.
- Examined osteoclast differentiation from bone marrow monocytes (BMMs).
- Analyzed the impact of c-Jun phosphorylation site mutations and c-Jun/JunD deficiencies.
Main Results:
- JNK1, not JNK2, is activated by RANKL and required for osteoclastogenesis.
- JNK1 protects BMMs from RANKL-induced apoptosis during differentiation.
- Efficient osteoclastogenesis requires c-Jun phosphorylation and c-Jun, but not JunD.
Conclusions:
- JNK1 activation is critical for osteoclastogenesis via RANKL signaling.
- JNK1 influences osteoclast differentiation through both c-Jun phosphorylation-dependent and -independent pathways.
- JNK1's anti-apoptotic role in BMMs is independent of c-Jun phosphorylation.