Augmenting MNK1/2 activation by c-FMS proteolysis promotes osteoclastogenesis and arthritic bone erosion
| Autor: | Jong Dae Ji, Steven Zeng, Carmen Chai, Se Hwan Mun, Matthew Jundong Kim, Haemin Kim, Tae-Hwan Kim, Brian Oh, Kyung-Hyun Park-Min, Younseo Oh, Chitra Lekha Dahia, Seyeon Bae, George D. Kalliolias |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Macrophage colony-stimulating factor
Histology Myeloid medicine.diagnostic_test Chemistry QH301-705.5 Physiology Endocrinology Diabetes and Metabolism Inflammatory arthritis Proteolysis medicine.disease Bone resorption Article Cell biology Bone remodeling Bone quality and biomechanics medicine.anatomical_structure Osteoclast medicine QP1-981 Biology (General) Receptor Bone |
| Zdroj: | Bone Research Bone Research, Vol 9, Iss 1, Pp 1-11 (2021) |
| ISSN: | 2095-6231 2095-4700 |
| Popis: | Osteoclasts are bone-resorbing cells that play an essential role in homeostatic bone remodeling and pathological bone erosion. Macrophage colony stimulating factor (M-CSF) is abundant in rheumatoid arthritis (RA). However, the role of M-CSF in arthritic bone erosion is not completely understood. Here, we show that M-CSF can promote osteoclastogenesis by triggering the proteolysis of c-FMS, a receptor for M-CSF, leading to the generation of FMS intracellular domain (FICD) fragments. Increased levels of FICD fragments positively regulated osteoclastogenesis but had no effect on inflammatory responses. Moreover, myeloid cell-specific FICD expression in mice resulted in significantly increased osteoclast-mediated bone resorption in an inflammatory arthritis model. The FICD formed a complex with DAP5, and the FICD/DAP5 axis promoted osteoclast differentiation by activating the MNK1/2/EIF4E pathway and enhancing NFATc1 protein expression. Moreover, targeting the MNK1/2 pathway diminished arthritic bone erosion. These results identified a novel role of c-FMS proteolysis in osteoclastogenesis and the pathogenesis of arthritic bone erosion. |
| Databáze: | OpenAIRE |
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