Hematopoietic or Osteoclast-Specific Deletion of Syk Leads to Increased Bone Mass in Experimental Mice

Discussion In this manuscript, we provide direct genetic evidence for the role of the Syk tyrosine kinase in normal bone homeostasis in adult mice. The perinatal lethality of Syk−/− mice was overcome by lineage-specific conditional deletion of Syk in osteoclasts (SykΔOC mice) or in the entire hematopoietic system (SykΔHaemo mice). Both osteoclast-specific and hematopoietic Syk deletion led to increased trabecular bone mass and defective in vitro osteoclast development and function. However, hematopoietic Syk deletion caused more robust changes than osteoclast-specific Syk deletion both in vivo and in vitro. Our results suggest that this is due to late and incomplete deletion of Syk in osteoclast-specific Syk mutants, likely caused by late activation and modest activity of Cre expression driven by the Ctsk gene promoter during osteoclast development. We and others have previously shown that Syk plays an important role in in vitro osteoclast development and osteoclast-mediated resorptive activity (40, 42, 44). However, the role of Syk in bone homeostasis in live mice could not be tested because of the perinatal lethality of Syk−/− mice (17, 18), although bone density appeared to be increased in third-trimester Syk−/− fetuses (44). Unfortunately, the in vitro osteoclast phenotypes cannot be directly extrapolated to the in vivo situation since a number of mutations even within the same pathway, such as DAP12 (38, 4...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research