Mice with a disruption of the thrombospondin 3 gene differ in geometric and biomechanical properties of bone and have accelerated development of the femoral head.
Thrombospondin 3 (TSP3) is structurally similar to cartilage oligomeric matrix protein (COMP/TSP5), but its function is unknown. To determine the functional significance of TSP3, we generated mice with a targeted disruption of Thbs3. TSP3-null mice are viable and fertile and show normal prenatal skeletal patterning, based on Alcian blue/Alizarin red S staining. However, subtle and transient abnormalities were detected in the developing postnatal skeleton. Young adult TSP3-null mice are heavier than controls, and analyses of the geometric and biomechanical properties of long bones show increases in the moments of inertia, endocortical and periostal radii, and failure load. The bones of 9-week-old TSP3-null male mice also have a significantly greater cortical area. Most of these differences were no longer detected in 15-week-old mice. Micro-computed tomography scans showed that the trabecular bone proximal to the femoral head growth plate developed at an earlier time in TSP3-null mice than in wild-type mice. Thus, vascular invasion and ossification start in the femoral heads of TSP3-null mice at 9 weeks, whereas the wild-type femoral head is still composed of hypertrophic chondroctyes in a calcified matrix at 15 weeks. These results provide evidence for a role for TSP3 in the regulation of skeletal maturation in mice.
Hankenson
Kurt D
KD
Department of Orthopaedic Surgery, and Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
Hormuzdi
Sheriar G
SG
Meganck
Jeffrey A
JA
Bornstein
Paul
P
D000818:Animals; D001696:Biomechanical Phenomena; D001846:Bone Development; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000196:embryology* / Q000502:physiology; D005270:Femur Head / Q000000981:diagnostic imaging / Q000254:growth & development*; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D010012:Osteogenesis / Q000502:physiology*; D019699:Thrombospondins / Q000235:genetics* / Q000378:metabolism*; D013997:Time Factors; D014057:Tomography, X-Ray Computed
D019699:Thrombospondins; C101863:thrombospondin 3