High bone mass in the STR/ort mouse results from increased bone formation and impaired bone resorption and is associated with extramedullary hematopoiesis
- 409 Downloads
We here describe the novel high bone mass phenotype in STR/ort mice that leads to increased bone masses of cortical and trabecular bone and is associated with elevated osteoblast activity and impaired osteoclast function alike. Comparison of STR/ort and C57BL/6 mice reveals an increase in trabecular bone volumes of the vertebrae and at femoral metaphysis. In the females, this difference is significant as early as 2 months of age and at 9 months the females by far exceed their age matched males in all parameters measured. The increase in cortical bone mass at femoral diaphysis results from an apposition to the endosteal surface, it is significant for both sexes as early as 1 month of age and leads to bone marrow compression and extramedullary hematopoiesis. Altered activities of both, the osteoblast and the osteoclast contribute to the high bone mass and collectively this phenotype supports a multifactorial pathogenesis. Moreover, the spontaneous development of osteoarthritis in male STR/ort mice is suggestive of a tight correlation between trabecular bone mass and the development of degenerative changes of the articular cartilage.
KeywordsHigh bone mass Histomorphometry X-ray micro-computed tomography (μCT) Extramedullary hematopoiesis
This work was supported by grants from the German Research Foundation (DFG, MU 844/12-1) and the University of Rostock (FORUN). The authors would like to thank Marlies Dettmer (Institute of Immunology), Dorothea Frenz and Ilona Klamfuß (both of the Institute of Experimental Surgery) for expert technical assistance and Karin Gerber (Institute of Experimental Surgery) for taking excellent care of the animals. Special thanks go to Philipp Herlyn and Dagmar-Christiane Fischer for their support with the X-ray micro-computed tomography and to Bettina Willie for her help with the TRAcP stainings. We are also grateful for fruitful discussions with Brigitte Vollmar.
Conflict of interest
All authors have no conflicts of interest.
- 5.Dougall WC, Glaccum M, Charrier K, Rohrbach K, Brasel K, De Smedt T, Daro E, Smith J, Tometsko ME, Maliszewski CR, Armstrong A, Shen V, Bain S, Cosman D, Anderson D, Morrissey PJ, Peschon JJ, Schuh J (1999) RANK is essential for osteoclast and lymph node development. Genes Dev 13:2412–2424PubMedCrossRefGoogle Scholar
- 8.Teti A, Migliaccio S, Taranta A, Bernardini S, De Rossi G, Luciani M, Iacobini M, De Felice L, Boldrini R, Bosman C, Corsi A, Bianco P (1999) Mechanisms of osteoclast dysfunction in human osteopetrosis: abnormal osteoclastogenesis and lack of osteoclast-specific adhesion structures. J Bone Miner Res 14:2107–2117PubMedCrossRefGoogle Scholar
- 18.Del Fattore A, Peruzzi B, Rucci N, Recchia I, Cappariello A et al (2006) Clinical, genetic, and cellular analysis of 49 osteopetrotic patients: implications for diagnosis and treatment. J Med Genet 43:315–325Google Scholar
- 23.Schulze J, Seitz S, Saito H, Schneebauer M, Marshall RP, Baranowsky A, Busse B, Schilling AF, Friedrich FW, Albers J, Spiro AS, Zustin J, Streichert T, Ellwanger K, Niehrs C, Amling M, Baron R, Schinke T (2010) Negative regulation of bone formation by the transmembrane Wnt antagonist Kremen-2. PLoS ONE 5:e10309PubMedCrossRefGoogle Scholar
- 31.Van Wesenbeeck L, Odgren PR, Coxon FP, Frattini A, Moens P, Perdu B, MacKay CA, Van Hul E, Timmermans JP, Vanhoenacker F, Jacobs R, Peruzzi B, Teti A, Helfrich MH, Rogers MJ, Villa A, Van Hul W (2007) Involvement of PLEKHM1 in osteoclastic vesicular transport and osteopetrosis in incisors absent rats and humans. J Clin Invest 117:919–930PubMedCrossRefGoogle Scholar