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Effect of Reduced c‐Kit Signaling on Bone Marrow Adiposity
Author(s) -
Turner Russell T.,
Wong Carmen P.,
Iwaniec Urszula T.
Publication year - 2011
Publication title -
the anatomical record: advances in integrative anatomy and evolutionary biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.678
H-Index - 62
eISSN - 1932-8494
pISSN - 1932-8486
DOI - 10.1002/ar.21409
Subject(s) - adipogenesis , bone marrow , endocrinology , medicine , stromal cell , adipocyte , osteoblast , biology , chemistry , adipose tissue , biochemistry , in vitro
c‐Kit (CD117) is required for normal differentiation of osteoblasts from bone marrow stromal cells and for normal bone formation. Osteoblasts and adipocytes originate from a common progenitor cell, and a reciprocal relationship in differentiation of the two lineages is often observed. Therefore, the effects of abnormal c‐kit signaling on bone marrow adiposity and adipocyte precursor pool size were evaluated in mouse strains with loss of function mutations in kit receptor or kit ligand. Additionally, to determine whether short‐duration pharmacological disruption of kit signaling influences bone marrow adiposity, we administered the kit receptor antagonist gleevec (imatinib mesilate) for 1 week to middle aged (13‐month‐old) male rats known to have high levels of bone marrow fat. Compared to wild‐type littermates, adipocytes were absent and adipocyte precursors greatly reduced in bone marrow from kit receptor‐deficient Kit W/W‐ν mice. Administration of secreted kit ligand to membrane‐associated kit ligand‐deficient Kit Sl/Sl‐d mice was ineffective in inducing bone marrow adipogenesis. These findings suggest that activation of kit receptor by the membrane‐associated form of kit ligand is required for kit signaling to promote bone marrow adipogenesis in mice. Rats treated with gleevec had lower adipocyte density compared to age‐matched controls, suggesting that kit signaling is required to maintain normal bone marrow adiposity. Taken together, our results indicate that c‐Kit signaling plays an important but previously unsuspected role in regulating bone marrow adiposity. Anat Rec, , 2011. © 2011 Wiley‐Liss, Inc.

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