title: Disturbed synthesis of type II collagen interferes with rate of bone formation and growth and increases bone resorption in transgenic mice.
abstract: Transgenic mice carrying an internally deleted human type II collagen gene (COL2A1) were used to study bone growth and development. This mutation has previously been shown to disturb the development of collagen fibrils in articular cartilage, causing chondrodysplasia and osteoarthritis. Type II collagen expression in bones was investigated with immunohistochemistry. The development and mineralization of the skeleton and anthropometric measurements on bones were evaluated using X-rays and dynamic histomorphometry. Type II collagen was expressed in the cartilage of developing bones. The bones of transgenic mice were smaller compared with the controls. The bone mass remained almost unchanged in transgenic mice after 1 month of age, leading to differences of 47% in trabecular bone volume (P = 0.012) and 40% in trabecular thickness (P < 0.01) at the age of 3 months compared with controls. At the age of 3 months the eroded surface per bone volume was 31% greater in transgenic mice compared with controls (P < 0.05). Trabecular thickness correlated positively with body weight (R = 0.71, P < 0.001). Interestingly, body weight correlated with bone volume in control mice (R = 0.27, P < 0.01), but no correlation was observed in transgenic mice. The disturbed synthesis of cartilage-specific type II collagen in growing transgenic mice retarded bone development, increased bone resorption, and altered tissue properties. This led to a negative net bone balance and small bone size. The results support the idea that an altered synthesis of cartilage-specific molecule(s) can disturb postnatal bone development and growth.
authors.affiliation: Coxa Hospital for Joint Replacement, PO Box 652, FIN-33101 Tampere, Finland. jyrki.nieminen@coxa.fi
authors.forename: Jyrki
authors.initials: J
authors.lastname: Nieminen
authors.forename: Janne
authors.initials: J
authors.lastname: Sahlman
authors.forename: Teemu
authors.initials: T
authors.lastname: Hirvonen
authors.forename: Tuomo
authors.initials: T
authors.lastname: Lapveteläinen
authors.forename: Markku
authors.initials: M
authors.lastname: Miettinen
authors.forename: Ilkka
authors.initials: I
authors.lastname: Arnala
authors.forename: Hartmut H
authors.initials: HH
authors.lastname: Malluche
authors.forename: Heikki J
authors.initials: HJ
authors.lastname: Helminen
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D015519:Bone Density / Q000235:genetics; D001862:Bone Resorption / Q000235:genetics* / Q000378:metabolism; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000378:metabolism*; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D024043:Collagen Type II / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D018345:Mice, Knockout; D010012:Osteogenesis / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D011859:Radiography
chemical_list: D015415:Biomarkers; C447413:Col2a1 protein, mouse; D024043:Collagen Type II; D012333:RNA, Messenger