The cell surface form of colony-stimulating factor-1 is biologically active in bone in vivo.
The specific biological function of the cell surface or membrane-bound isoform of colony-stimulating factor-1 (mCSF-1) is not well understood. To help define the role of this isoform in bone, we developed a transgenic mouse in which targeted expression of human mCSF-1 in osteoblasts was achieved under the control of the 2.4-kb rat collagen type I alpha promoter. Bone density, determined by peripheral quantitative computed tomography, was reduced 7% in mCSF-1 transgenic compared with that in wild-type mice. Histomorphometric analyses indicated that the number of osteoclasts in bone (NOc/BPm, NOc/TAR, OcS/BS) was significantly increased in transgenic mice (1.7- to 1.8-fold; P < 0.05 to P < 0.01) compared with that in wild-type animals. Interestingly, the osteoblast-restricted isoform transgene corrected the osteopetrosis seen in CSF-1-deficient op/op mice. Skeletal growth and bone density in op/op mice expressing mCSF-1 in osteoblasts were similar to those in wild-type mice and were dramatically different from those in the unmanipulated op/op animals. The op/op mice expressing mCSF-1 in bone had normal incisor and molar tooth eruption, whereas the op/op mice evidenced the expected failure of tooth eruption. These findings directly support the conclusion that mCSF-1 is functionally active in bone in vivo and is probably an important local source of CSF-1.
Yao
Gang-Qing
GQ
Section of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8016, USA. gang-qing.yao@yale.edu
Wu
Jain-Jun
JJ
Sun
Ben-Hua
BH
Troiano
Nancy
N
Mitnick
Mary Ann
MA
Insogna
Karl
K
D000818:Animals; D015519:Bone Density; D001846:Bone Development; D001842:Bone and Bones / Q000502:physiology*; D002452:Cell Count; D024042:Collagen Type I / Q000235:genetics; D005269:Femur / Q000166:cytology; D015870:Gene Expression; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts; D010022:Osteopetrosis / Q000209:etiology / Q000628:therapy; D011401:Promoter Regions, Genetic; D051381:Rats; D014057:Tomography, X-Ray Computed
D024042:Collagen Type I; D016173:Macrophage Colony-Stimulating Factor