Journalartikel

Jahr der Veröffentlichung: 2014

Seiten: 765-777

Zeitschrift: The American Journal of Pathology

Bandnummer: 184

Heftnummer: 3

ISSN: 0002-9440

eISSN: 1525-2191

DOI Link: https://doi.org/10.1016/j.ajpath.2013.11.011

Verlag: Elsevier

Abstract: 
In estrogen-deficient, postmenopausal women, vitamin D and calcium deficiency increase osteoporotic fracture risk. Therefore, a new rat model of combined ovariectomy and multiple-deficient diet was established to mimic human postmenopausal osteoporotic conditions under nutrient deficiency. Sprague-Dawley rats were untreated (control), Laparatomized (sham), or ovariectomized and received a deficient diet (OVX-Diet). Multiple analyses involving structure (micro-computed tomography and biomechanics), cellutarity (osteoblasts and osteoclasts), bone matrix (mRNA expression and IHC), and mineralization were investigated for a detailed characterization of osteoporosis. The study involved tong-term observation up to 14 months (M14) after laparotomy or after OVX-Diet, with intermediate time points at M3 and M12. OVX-Diet rats showed enhanced osteoblastogenesis and osteoclastogenesis. Bone matrix markers (biglycan, COL1A1, tenascin C, and fibronectin) and low-density Lipoprotein-5 (bone mass marker) were down-regulated at M12 in OVX-Diet rats. However, up-regulation of matrix markers and existence of unmineraLized osteoid were seen at M3 and M14. Osteoclast markers (matrix metallopeptidase 9 and cathepsin K) were up-regulated at M14. Micro-computed tomography and biomechanics confirmed bone fragility of OVX-Diet rats, and quantitative RT-PCR revealed a higher turnover rate in the humerus than in lumbar vertebrae, suggesting enhanced bone formation and resorption in OVX-Diet rats. Such bone remodeling caused disturbed bone mineralization and severe bone loss, as reported in patients with high-turnover, postmenopausal osteoporosis. Therefore, this rat model may serve as a suitable tool to evaluate osteoporotic drugs and new biomaterials or fracture implants.

Harvard-Zitierstil: Govindarajan, P., Boecker, W., El Khassawna, T., Kampschulte, M., SchLewitz, G., Huerter, B., et al. (2014) Bone Matrix, Cellularity, and Structural Changes in a Rat Model with High-Turnover Osteoporosis Induced by Combined Ovariectomy and a Multiple-Deficient Diet, The American Journal of Pathology, 184(3), pp. 765-777. https://doi.org/10.1016/j.ajpath.2013.11.011

APA-Zitierstil: Govindarajan, P., Boecker, W., El Khassawna, T., Kampschulte, M., SchLewitz, G., Huerter, B., Sommer, U., Duerselen, L., Ignatius, A., Bauer, N., Szalay, G., Wenisch, S., Lips, K., Schnettler, R., Langheinrich, A., & Heiss, C. (2014). Bone Matrix, Cellularity, and Structural Changes in a Rat Model with High-Turnover Osteoporosis Induced by Combined Ovariectomy and a Multiple-Deficient Diet. The American Journal of Pathology. 184(3), 765-777. https://doi.org/10.1016/j.ajpath.2013.11.011