| First Author | Wang CJ | Year | 2008 |
| Journal | J Bone Miner Res | Volume | 23 |
| Issue | 6 | Pages | 837-49 |
| PubMed ID | 18251701 | Mgi Jnum | J:150168 |
| Mgi Id | MGI:3849813 | Doi | 10.1359/jbmr.080214 |
| Citation | Wang CJ, et al. (2008) Trabecular bone deterioration in col9a1+/- mice associated with enlarged osteoclasts adhered to collagen IX-deficient bone. J Bone Miner Res 23(6):837-49 |
| abstractText | INTRODUCTION: Short collagen IX, the exclusive isoform expressed by osteoblasts, is synthesized through alternative transcription of the col9a1 gene. The function of short collagen IX in bone was characterized in col9a1-null mutant mice. MATERIALS AND METHODS: Trabecular bone morphometry of lumbar bones and tibias was evaluated by muCT and nondecalcified histology. Osteoblastic and osteoclastic activities were evaluated by PCR- and microarray-based gene expression assays and TRACP-5b and C-terminal telopeptide (CTX) assays, as well as in vitro using bone marrow stromal cells and splenocytes. The effect of col9a1(+/-) mutation on osteoclast morphology was evaluated using RAW264.7-derived osteoclastic cells cultured on the mutant or wildtype calvarial bone substrates. RESULTS: Col9a1 knockout mutation caused little effects on the skeletal development; however, young adult female col9a1(-/-) and col9a1(+/-) mice exhibited significant loss of trabecular bone. The trabecular bone architecture was progressively deteriorated in both male and female heterozygous col9a1(+/-) mice while aging. The aged mutant mice also exhibited signs of thoracic kyphosis and weight loss, resembling the clinical signs of osteoporosis. The col9a1(+/-) osteoblasts synthesized short col9a1 transcripts at decreased rates. Whereas bone formation activities in vitro and in vivo were not affected, the mutant osteoblast expressed the elevated ratio of RANKL/osteoprotegerin. Increased serum TRACP-5b and CTX levels were found in col9a1(+/-) mice, whose bone surface was associated with osteoclastic cells that were abnormally flattened and enlarged. The mutant and wildtype splenocytes underwent similar osteoclastogenesis in vitro; however, RAW264.7-derived osteoclastic cells, when cultured on the col9a1(+/-) calvaria, widely spread over the bone surface and formed large resorption pits. The surface of col9a1(+/-) calvaria was found to lack the typical nanotopography. CONCLUSIONS: The mineralized bone matrix deficient of short collagen IX may become susceptible to osteoclastic bone resorption, possibly through a novel non-cell-autonomous mechanism. The data suggest the involvement of bone collagen IX in the pathogenesis of osteoporosis. |
