Stanniocalcin 1 alters muscle and bone structure and function in transgenic mice.
Fish stanniocalcin (STC) inhibits uptake of calcium and stimulates phosphate reabsorption. To determine the role of the highly homologous mammalian protein, STC-1, we created and characterized transgenic mice that express STC-1 under control of a muscle-specific promoter. STC-1 transgenic mice were smaller than wild-type littermates and had normal growth plate cartilage morphology but increased cartilage matrix synthesis. In STC-1 mice, the rate of bone formation, but not bone mineralization, was decreased. Increased cortical bone thickness and changes in trabeculae number, density, and thickness in STC-1 mice indicated a concomitant suppression of osteoclast activity, which was supported by microcomputed tomography analyses and histochemistry. Skeletal muscles were disproportionately small and showed altered function and response to injury in STC-1 mice. Electron microscopy indicated that muscle mitochondria were dramatically enlarged in STC-1 mice. These changes in STC-1 mice could not be explained by deficits in blood vessel formation, as vascularity in organs and skeletal tissues was increased as was induction of vascularity in response to femoral artery ligation. Our results indicate that STC-1 can affect calcium homeostasis, bone and muscle mass and structure, and angiogenesis through effects on osteoblasts, osteoclasts, myoblasts/myocytes, and endothelial cells.
Department of Molecular Oncology, Genentech Inc., South San Francisco, California 94080, USA. filvarof@gene.com
Ellen H
EH
Filvaroff
Susan
S
Guillet
Constance
C
Zlot
Min
M
Bao
Gladys
G
Ingle
Hope
H
Steinmetz
John
J
Hoeffel
Stuart
S
Bunting
Jed
J
Ross
Richard A D
RA
Carano
Lyn
L
Powell-Braxton
Graham F
GF
Wagner
Renee
R
Eckert
Mary E
ME
Gerritsen
Dorothy M
DM
French
D000818:Animals; D001823:Body Composition; D001824:Body Constitution; D015519:Bone Density; D001846:Bone Development; D001857:Bone Matrix / Q000378:metabolism; D001842:Bone and Bones / Q000033:anatomy & histology* / Q000502:physiology*; D002113:Calcification, Physiologic; D002118:Calcium / Q000097:blood; D002356:Cartilage / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics / Q000502:physiology*; D006128:Growth / Q000235:genetics; D006132:Growth Plate / Q000033:anatomy & histology; D006728:Hormones / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D018482:Muscle, Skeletal / Q000033:anatomy & histology* / Q000502:physiology*; D018919:Neovascularization, Physiologic; D010010:Osteoclasts / Q000502:physiology; D012886:Skull / Q000000981:diagnostic imaging; D014057:Tomography, X-Ray Computed
D006023:Glycoproteins; D006728:Hormones; C051795:teleocalcin; D002118:Calcium