Academic Journal
Augmenting MNK1/2 activation by c-FMS proteolysis promotes osteoclastogenesis and arthritic bone erosion
| العنوان: | Augmenting MNK1/2 activation by c-FMS proteolysis promotes osteoclastogenesis and arthritic bone erosion |
|---|---|
| المؤلفون: | Se Hwan Mun, Seyeon Bae, Steven Zeng, Brian Oh, Carmen Chai, Matthew Jundong Kim, Haemin Kim, George Kalliolias, Chitra Lekha Dahia, Younseo Oh, Tae-Hwan Kim, Jong Dae Ji, Kyung-Hyun Park-Min |
| المصدر: | Bone Research, Vol 9, Iss 1, Pp 1-11 (2021) |
| بيانات النشر: | Nature Publishing Group, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Biology (General) LCC:Physiology |
| مصطلحات موضوعية: | Biology (General), QH301-705.5, Physiology, QP1-981 |
| الوصف: | Abstract 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2095-6231 |
| Relation: | https://doaj.org/toc/2095-6231 |
| DOI: | 10.1038/s41413-021-00162-0 |
| URL الوصول: | https://doaj.org/article/3a5bddf68ff148bea59fec14bf85d5e3 |
| رقم الانضمام: | edsdoj.3a5bddf68ff148bea59fec14bf85d5e3 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 20956231 |
|---|---|
| DOI: | 10.1038/s41413-021-00162-0 |