Stanniocalcin 1 Alters Muscle and Bone Structure and Function in Transgenic Mice

• Published in: Endocrinology (Philadelphia) Vol. 143; no. 9; pp. 3681 - 3690
• Main Authors: Filvaroff, Ellen H, Guillet, Susan, Zlot, Constance, Bao, Min, Ingle, Gladys, Steinmetz, Hope, Hoeffel, John, Bunting, Stuart, Ross, Jed, Carano, Richard A. D, Powell-Braxton, Lyn, Wagner, Graham F, Eckert, Renee, Gerritsen, Mary E, French, Dorothy M
• Format: Journal Article
• Language: English
• Published: United States Endocrine Society 01-09-2002; Oxford University Press
• Subjects: Angiogenesis; Animals; Blood vessels; Body Composition; Body Constitution; Bone and Bones - anatomy & histology; Bone and Bones - physiology; Bone Density; Bone Development; Bone growth; Bone mass; Bone matrix; Bone Matrix - metabolism; Calcification, Physiologic; Calcium; Calcium - blood; Calcium homeostasis; Calcium influx; Calcium phosphates; Cartilage; Cartilage - metabolism; Computed tomography; Cortical bone; Electron microscopy; Endothelial cells; Female; Femoral artery; Gene Expression; Glycoproteins - genetics; Glycoproteins - physiology; Growth - genetics; Growth plate; Growth Plate - anatomy & histology; Histochemistry; Homeostasis; Hormones - genetics; Hormones - physiology; Injury analysis; Male; Mice; Mice, Transgenic; Microscopy, Electron; Mineralization; Muscle, Skeletal - anatomy & histology; Muscle, Skeletal - physiology; Muscles; Myoblasts; Myocytes; Neovascularization, Physiologic; Osteoclasts; Osteoclasts - physiology; Osteogenesis; Protein structure; Skeletal muscle; Skull - diagnostic imaging; teleocalcin; Thickness; Tomography, X-Ray Computed; Transgenic animals; Transgenic mice
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2001-211424

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.