Objective: In the present study, our objective was to determine the role of MAPK phosphatase-1 (MKP-1) in osteoclastogenesis in defined osteoclast progenitor populations.
Method: Osteoclast progenitor cells were flushed from bone marrow of WT and MKP-1 KO mice and sorted into CD11bhi (Macrophage (MΦ)), CD11blo (MΦ lineage), and CD11b- (non-MΦ) populations and stained for M-CSF Receptor (CD115) and stem cell marker c-kit (CD117). Defined populations were plated for TRAP staining and RNA expression via RT-qPCR in response to M-CSF or M-CSF+RANKL for 3, 5, 7 and 9 days.
Result: Sorting and immunophenotyping revealed that KO mice had significantly reduced expression and altered distribution of CD11b, CD115 and CD117 in each sorted population compared to sorted WT controls. TRAP staining results indicate that cells depleted of CD11b (low/neg) were more highly osteoclastogenic and larger in KO populations compared to control. Finally, OC markers NFATc1, DCSTAMP, cathepsin k and calcitonin receptor showed significant differences between sorted groups and in WT vs KO.
Conclusion: Taken together, our data indicates that osteoclastogenesis is enhanced in low/neg cells. Moreover, MKP-1 KO low/neg populations had increased OC number and size indicating that some hematopoetic lineage subsets are greatly affected by the absence of MKP-1 than others during ostoclastogenesis.
Keywords: Immunology, Osteoblasts/osteoclasts, Progenitors and Resorption
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