Journal Facts

Journal
BoneKEy Knowledge Environment
ISSN
1533-4368
Volume
Year
2003

Article Facts

Title
Clinical and basic research papers: July 2003 selections
DOI
10.1138/2003098
Authors

Online Date
09/15/2003

Article Links

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Clinical and basic research papers: July 2003 selections


DOI:10.1138/2003098

Bone modeling and remodeling

◆ Daci E, Everts V, Torrekens S, Van Herck E, Tigchelaar-Gutterr W, Bouillon R, Carmeliet G. Increased bone formation in mice lacking plasminogen activators. J Bone Miner Res. 2003 Jul;18(7):1167–76.

Recommended. —ES

◆ Faccio R, Novack DV, Zallone A, Ross FP, Teitelbaum SL. Dynamic changes in the osteoclast cytoskeleton in response to growth factors and cell attachment are controlled by b3 integrin. J Cell Biol. 2003 Aug 4;162(3):499–509.

Osteoclast function requires avb3 integrin, the vitronectin receptor. This paper reports that mutant forms of avb3 that lack the cytoplasmic tail of b3 or the critical serine residue S752 are not normally activated by inside-out signaling induced by growth factors such as M-CSF. Failure to form the activated state of avb3 impairs phosphorylation of the tyrosine kinases c-Src and c_Cbl and recruitment of Rac and Rho, and thereby prevents cytoskeletal reorganization that is necessary for adhesion, migration and bone resorption. —GJS

◆ Kawano H, Sato T, Yamada T, Matsumoto T, Sekine K, Watanabe T, Nakamura T, Fukuda T, Yoshimura K, Yoshizawa T, Aihara K, Yamamoto Y, Nakamichi Y, Metzger D, Chambon P, Nakamura K, Kawaguchi H, Kato S. Suppressive function of androgen receptor in bone resorption. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9416–21.

Deletion of the androgen receptor (ARKO) produces a mouse model of the androgen insensitivity syndrome (complete testicular feminization). Bone mass is reduced in male mice and bone turnover is high. Yet bone size is normal. Testosterone levels are reduced and the phenotype is partially rescued by treatment with testosterone. In coculture, ARKO osteoblasts express high levels of RANKL and induce increased osteoclast formation. Female ARKO mice are normal, implying that estrogen effects on bone predominate in females. It thus appears that androgens are an important determinant of bone mineral density but not of bone size in the male mouse. —GJS

◆ O'Brien FJ, Taylor D, Lee TC. Microcrack accumulation at different intervals during fatigue testing of compact bone. J Biomech. 2003 Jul;36(7):973–80.

Microdamage is in, like apoptosis and knockouts, in fashion, but we know little about the effect of microdamage on compressive, tensile or torsional strength of whole bone, or the effects on bone toughness. The structural and material properties of bone that facilitate the development, extent of propagation longitudinally and radially direction need to be defined.

◆ Safadi FF, Xu J, Smock SL, Kanaan RA, Selim AH, Odgren PR, Marks SC Jr, Owen TA, Popoff SN. Expression of connective tissue growth factor in bone: its role in osteoblast proliferation and differentiation in vitro and bone formation in vivo. J Cell Physiol. 2003 Jul;196(1):51–62.

Recommended. —ES

Pathophysiology

◆ Yamamoto N, Sakai F, Kon S, Morimoto J, Kimura C, Yamazaki H, Okazaki I, Seki N, Fujii T, Uede T. Essential role of the cryptic epitope SLAYGLR within osteopontin in a murine model of rheumatoid arthritis. J Clin Invest. 2003 Jul;112(2):181–8. See also: Gravallese EM. Osteopontin: a bridge between bone and the immune system. J Clin Invest. 2003 Jul;112(2):147–9.

Osteopontin is important both in bone resorption and in the immune system, where it has pleiotropic functions as a cytokine critical for the generation of Th1 immunity. Thrombin cleavage exposes a cryptic osteopontin epitope, SLAYGLR. It is here shown that antibodies to SLAYGR block the development of arthritis in a murine model of rheumatoid arthritis. But as the editorial points out, the antibody may have other effects on the immune system. —GJS

Physiology and metabolism

◆ Danks JA, Ho PM, Notini AJ, Katsis F, Hoffmann P, Kemp BE, Martin TJ, Zajac JD. Identification of a parathyroid hormone in the fish Fugu rubripes. J Bone Miner Res. 2003 Jul;18(7):1326–31.

The question is where does the PTH come from in fish - the thymus? the Organ of Stannius? Could the very different sequence of this PTH offer options for new analogs for the treatment of osteoporosis? We need anabolic agents at reduced cost.

◆ Khokha MK, Hsu D, Brunet LJ, Dionne MS, Harland RM. Gremlin is the BMP antagonist required for maintenance of Shh and Fgf signals during limb patterning. Nat Genet. 2003 Jul;34(3):303–7.

Recommended. —ES

Treatment and drug effects

◆ Teng M, Wolf M, Lowrie E, Ofsthun N, Lazarus JM, Thadhani R. Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy. N Engl J Med. 2003 Jul 31;349(5):446–56.

Secondary hyperparathyroidism and a high calcium-phosphate product appear to be associated with increased mortality in dialysis patients. In this retrospective analysis of over 60,000 dialysis patients, mortality was significantly less in patients treated with intravenous paricalcitol (19-nor-1,25-dihydroxyvitaminD2) than in patients treated with intravenous calcitriol. The mortality benefit of paricalcitol treatment was independent of calcium or PTH levels and the pathophysiological basis of the mortality difference remains to be explained. —GJS

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