Selective deletion of the membrane-bound colony stimulating factor 1 isoform leads to high bone mass but does not protect against estrogen-deficiency bone loss
Copyright policy )Selective deletion of the membrane-bound colony stimulating factor 1 isoform leads to high bone mass but does not protect against estrogen-deficiency bone loss
To better define the biologic function of membrane-bound CSF1 (mCSF1) in vivo, we have generated mCSF1 knockout (k/o) mice. Spinal bone density (BMD) was 15.9% higher in k/o mice compared to wild-type (wt) controls (P < 0.01) and total BMD was increased by 6.8% (P < 0.05). A higher mean femur BMD was also observed but did not reach statistical significance (6.9% P = NS). The osteoclastogenic potential of bone marrow isolated from mCSF1 k/o mice was reduced compared to wt marrow. There were no defects in osteoblast number or function suggesting that the basis for the high bone mass phenotype was reduced resorption. In addition to a skeletal phenotype, k/o mice had significantly elevated serum triglyceride levels (123 ± 7 vs. 88 ± 3.2 mg/dl; k/o vs. wt, P < 0.001), while serum cholesterol levels were similar (122 ± 6 vs. 116 ± 6 mg/dl; k/o vs. wt, P = NS). One month after surgery, 5-month-old k/o and wt female mice experienced the same degree of bone loss following ovariectomy (OVX). OVX induced a significant fourfold increase in the expression of the soluble CSF1 isoform (sCSF1) in the bones of wt mice while expression of mCSF1 was unchanged. These findings indicate that mCSF1 is essential for normal bone remodeling since, in its absence, BMD is increased. Membrane-bound CSF1 does not appear to be required for estrogen-deficiency bone loss while in contrast; our data suggest that sCSF1 could play a key role in this pathologic process. The reasons why mCSF1 k/o mice have hypertriglyceridemia are currently under study.
- Yale University United States
Hypertriglyceridemia, Male, Mice, Knockout, Sex Characteristics, Osteoblasts, Osteoclasts, Cell Differentiation, Bone and Bones, Coculture Techniques, Mice, Colony-Stimulating Factors, Bone Density, Animals, Humans, Osteoporosis, Protein Isoforms, Female, RNA, Messenger, Cells, Cultured, Osteoporosis, Postmenopausal
Hypertriglyceridemia, Male, Mice, Knockout, Sex Characteristics, Osteoblasts, Osteoclasts, Cell Differentiation, Bone and Bones, Coculture Techniques, Mice, Colony-Stimulating Factors, Bone Density, Animals, Humans, Osteoporosis, Protein Isoforms, Female, RNA, Messenger, Cells, Cultured, Osteoporosis, Postmenopausal
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