scholarly journals Augmenting MNK1/2 activation by c-FMS proteolysis promotes osteoclastogenesis and arthritic bone erosion

Bone Research ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Se Hwan Mun ◽  
Seyeon Bae ◽  
Steven Zeng ◽  
Brian Oh ◽  
Carmen Chai ◽  
...  
Keyword(s):  
Inflammatory Arthritis ◽  
Essential Role ◽  
Inflammatory Responses ◽  
Bone Erosion ◽  
Osteoclast Differentiation ◽  
Myeloid Cell ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

AbstractOsteoclasts 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.

scholarly journals Role of Synovial Exosomes in Osteoclast Differentiation in Inflammatory Arthritis

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 120
Author(s):  
Ji Eun Song ◽  
Ji Soo Kim ◽  
Ji Hye Shin ◽  
Ki Won Moon ◽  
Jin Kyun Park ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Inflammatory Arthritis ◽  
Mononuclear Cells ◽  
Osteoclast Differentiation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tartrate Resistant Acid Phosphatase ◽  
Healthy Donors ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony

This study aimed to investigate the characteristics of exosomes isolated from synovial fluid and their role in osteoclast differentiation in different types of inflammatory arthritis. Exosomes isolated from synovial fluid of rheumatoid arthritis (RA), ankylosing spondylitis (AS), gout, and osteoarthritis (OA) patients were co-incubated with CD14+ mononuclear cells from healthy donors without macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B ligand (RANKL). Osteoclast differentiation was evaluated via tartrate-resistant acid phosphatase (TRAP) staining and activity and F-actin ring formation. RANKL expression on synovial exosomes was assessed using flow cytometry and an enzyme-linked immunosorbent assay (ELISA). Synovial exosomes were the lowest in OA patients; these induced osteoclastogenesis in the absence of M-CSF and RANKL. Osteoclastogenesis was significantly higher with more exosomes in RA (p = 0.030) than in OA patients, but not in AS or gout patients. On treating macrophages with a specified number of synovial exosomes from RA/AS patients, exosomes induced greater osteoclastogenesis in RA than in AS patients. Synovial exosomal RANKL levels were significantly higher in RA (p = 0.035) than in AS patients. Synovial exosome numbers vary with the type of inflammatory arthritis. Synovial exosomes from RA patients may bear the disease-specific “synovial signature of osteoclastogenesis.”

scholarly journals Essential role of macrophage colony-stimulating factor in the osteoclast differentiation supported by stromal cells.

1991 ◽  
Vol 173 (5) ◽  
pp. 1291-1294 ◽  
Author(s):  
H Kodama ◽  
M Nose ◽  
S Niida ◽  
A Yamasaki
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Bone Marrow Cells ◽  
Osteoclast Differentiation ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Marrow Cells

Severe deficiency of osteoclasts, monocytes, and peritoneal macrophages in osteopetrotic (op/op) mutant mice is caused by the absence of functional macrophage colony-stimulating factor (M-CSF). To clarify the role of M-CSF in the osteoclast differentiation, we established a clonal stromal cell line OP6L7 capable of supporting hemopoiesis from newborn op/op mouse calvaria. Although very few macrophages appeared in the cocultures of bone marrow cells and OP6L7 cells, a 50-fold larger number of macrophages was detected in the day 7 cocultures when purified recombinant human M-CSF (rhM-CSF) was exogenously supplied. Tartrate-resistant acid phosphatase (TRACP; a marker enzyme of osteoclasts)-positive cells appeared only when bone marrow cells were cultured in contact with OP6L7 cells and both rhM-CSF and 1 alpha, 25 (OH)2D3 were added. The TRACP-positive cells became multinucleated with increasing time in culture and expressed the c-fms/M-CSF receptor. These results indicate that both contact with stromal cells and M-CSF are requisite for osteoclast differentiation under physiological conditions.

Role of Endogenous Granulocyte-Macrophage Colony Stimulating Factor Following Stroke and Relationship to Neurological Outcome

2009 ◽  
Vol 6 (4) ◽  
pp. 246-251 ◽  
Author(s):  
Miriam Navarro-Sobrino ◽  
Anna Rosell ◽  
Anna Penalba ◽  
Marc Ribo ◽  
Jose Alvarez-Sabin ◽  
...  
Keyword(s):  
Neurological Outcome ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor
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