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fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
Miao, Dengshun; Scutt, Andrew (2002)
Languages: English
Types: Article
Subjects: RC
Background\ud \ud Although much is known about the regulation of osteoclast (OC) formation and activity, little is known about OC senescence. In particular, the fate of of OC seen after 1,25-(OH)2D3 administration in vivo is unclear. There is evidence that the normal fate of OC is to undergo apoptosis (programmed cell death). We have investigated the effect of short-term application of high dose 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on OC apoptosis in an experimental rat model.\ud \ud Methods\ud \ud OC recruitment, augmentation and apoptosis was visualised and quantitated by staining histochemically for tartrate resistant acid phosphatase (TRAP), double staining for TRAP/ED1 or TRAP/DAPI, in situ DNA fragmentation end labelling and histomorphometric analysis.\ud \ud Results\ud \ud Short-term treatment with high-dose 1,25-(OH)2D3 increased the recruitment of OC precursors in the bone marrow resulting in a short-lived increase in OC numbers. This was rapidly followed by an increase in the number of apoptotic OC and their subsequent removal. The response of OC to 1,25-(OH)2D3 treatment was dose and site dependent; higher doses producing stronger, more rapid responses and the response in the tibiae being consistently stronger and more rapid than in the vertebrae.\ud \ud Conclusions\ud \ud This study demonstrates that (1) after recruitment, OC are removed from the resorption site by apoptosis (2) the combined use of TRAP and ED1 can be used to identify OC and their precursors in vivo (3) double staining for TRAP and DAPI or in situ DNA fragmentation end labelling can be used to identify apoptotic OC in vivo.\ud
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    • 1. Athanasou N: Cellular biology of bone-resorbing cells. J Bone Joint Surgam 1996, 78a:1096-1112
    • 2. Beelen R, Eestermans I, Döpp E, Dijkstra C: Monoclonal antibodies ED1, ED2 and ED3 against rat macrophages: expression of recognized antigens in different stages of differentiation. Transplant Proc 1987, 19:3166-3170
    • 3. Bianco P, Ballanti P, Bonucci E: Tartrate-resistant acid phosphatase activity in rat osteoblasts and osteocytes. Calcif Tissue Int 1988, 43:167-171
    • 4. Bollerslev J, Gram J, Nielsen HK, Brixen K, Storm T, Larsen HF, Mosekilde L: Effect of a short course of 1,25-dihydroxyvitamin D3 on biochemical markers of bone remodelling in adult male volunteers. Bone 1991, 12:339-343
    • 5. Bourque W, Gross M, Hall B: A histological processing technique that preserves the integrity of calcified tissues (bone, enamel), yolky amphibian embryos, and growth factor antigens in skeletal tissue. J Histochem Cytochem 1993, 41:1429-1434
    • 6. Boyce R, Weisbrode S: Histogenesis of hyperosteoidosis in 1,25(OH)2 D3-treated rats fed high levels of dietary calcium. Bone 1985, 6:105-112
    • 7. Damoiseaux JG, Döpp EA, Calame W, Chao D, MacPherson GG, Dijkstra CD: Rat macrophage lysosomal membrane antigen recognized by monoclonal antibody ED1. Immunology 1994, 83:140-147
    • 8. Dijkstra C, Döpp E, Joling P, Kraal G: The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in the rat recognized by monoclonal antibodies ED1, ED2 and ED3. Immunology 1985, 54:589-599
    • 9. Erben RG, Scutt AM, Miao D, Kollenkirchen U, Haberey M: Shortterm treatment of rats with high dose 1,25-dihydroxyvitamin D3 stimulates bone formation and increases the number of osteoblast precursor cells in bone marrow. Endocrinology 1997, 138:4629-4635
    • 10. Felix R, Cecchini M, Fleisch H: Macrophage colony stimulating factor restores in vivo bone resorption in the op/op osteopetrotic mouse. Endocrinology 1990, 127:2592-2594
    • 11. Felix R, Cecchini MG, Hofstetter W, Elford PR, Stutzer A, Fleisch H: Impairment of macrophage-stimulating factor production and lack of resident bone marrow macrophages in osteopetrotic op/op mouse. J Bone Miner Res 1990, 5:781-789
    • 12. Feyen J, Elford P, Padova FD, Trechsel U: Interleukin-6 is produced by bone and modulated by parathyroid hormone. J Bone Miner Res 1989, 4:633-638
    • 13. Fischman D, Hay E: Origin of osteoclasts from mononuclear leucocytes in regenerating new limbs. Anat Rec 1962, 143:329- 334
    • 14. Gallagher JC, Jerpbak CM, Jee WS, Johnson KA, DeLuca HF, Riggs BL: 1,25-dihydroxyvitamin D3: Short- and long-time effects on bone and calcium metabolism in patients with postmenopausal osteoporosis. Proc Natl Acad Sci USA 1982, 79:3325-3329
    • 15. Geusens P, Vanderschueren D, Verstraeten A, Dequeker J, Devos P, Bouillon R: Short-term course of 1,25(OH)2D3 stimulates osteoblasts but not osteoclasts in osteoporosis and osteoarthritis. Calcif Tissue Int 1991, 49:168-173
    • 16. Gram J, Junker P, Nielsen H, Bollerslev J: Dose-response effect of short-term calcitriol treatment on bone and mineral metabolism in normal males. Bone 1996, 18:539-544
    • 17. Hattersley G, Kerby J, Chambers T: Identification of osteoclast precursors in multilineage hemopoietic colonies. Endocrinology 1991, 128:259-262
    • 18. Hattersley G, Owens J, Flanagan A, Chambers T: Macrophage colony stimulating factor (M-CSF) is essential for osteoclast formation in vitro. Biochem Biophys Res Commun 1991, 177:526-531
    • 19. Hauschka P, Mavrakos A, Iafrati MD, Doleman SE, Klagsbrun M: Growth factors in bone matrix, isolation of multiple types by affinity chromatography on heparin-sepharose. J Biol Chem 1986, 261:12665-12674
    • 20. Holtrop M, Raisz L: Comparison of the effects of 1,25-dihydroxycholecalciferol, prostaglandin E2 and osteoclast activating factor with parathyroid hormone on the ultrastructure of osteoclasts in cultural long bone of fetal rats. Calcif Tissue Int 1979, 29:201-205
    • 21. Hughes D, Dai A, Tiffee JC, Li HH, Mundy GR, Boyce BF: Estrogen Promotes apoptosis of murine osteoclasts mediated by TGF-β. Nat Med 1996, 2:1132-1136
    • 22. Jäger A, Radlanski R, Götz W: Demonstration of cells of the mononuclear phagocyte lineage in the periodontium following experimental tooth movement in the rat - An immunohistochemical study using monoclonal antibodies ED1 and ED2 on paraffin-embedded tissues. Histochemistry 1993, 100:161-166
    • 23. Kahn A, Simmons D: Investigation of cell lineage in bone using a chimera of chick and quail embryonic tissue. Nature 1975, 258:325-327
    • 24. Kitazawa R, Kitazawa S: Vitamin D(3) augments osteoclastogenesis via vitamin D-responsive element of mouse RANKL gene promoter. Biochem Biophys Res Commun 2002, 290:650- 655
    • 25. Kobayashi Y, Hashimoto F, Miyamoto H, Kanaoka K, Miyazaki-Kawashita Y, Nakashima T, Shibata M, Kobayashi K, Kato Y, Sakai H: Forceinduced osteoclast apoptosis in vivo is accompanied by elevation in transforming growth factor and osteoprotegerin expression. J Bone Miner Res 2000, 15:1924-1934
    • 26. Manolagas S, Provvedini D, Tsoukas C: Interactions of 1,25-dihydroxyvitamin D3 and the immune system. Mol Cell Endocrinol 1985, 43:113-122
    • 27. Marks S, Walker D: The hematogeneous origin of osteoclasts: Experimental evidence from osteopetrotic (microphtalmic) mice treated with spleen cells from beige mouse donors. Am J Anat 1981, 161:1-10
    • 28. McLean I, Nakane P: Periodate-lysine-paraformaldehyde fixative a new fixative immunoelectron microscopy. J Histochem Cytochem 1974, 22:1077-1083
    • 29. McSheehy P, Chambers T: 1,25-dihydroxyvitamin D3 stimulates rat osteoblastic cells to release a soluble factor that increases osteoclastic resorption. J Clin Invest 1987, 80:425-429
    • 30. Merke J, Klaus G, Hugel R, Waldherr R, Ritz E: No 1,25-dihydroxyvitamin D3 receptors on osteoclasts of calcium-deficient chicken despite demonstrable receptors on circulating monocytes. J Clin Invest 1986, 77:312-314
    • 31. Mori S, Sawai T, Teshima T, Kyogoku M: A new decalcifying technique for immunohistochemical studies of calcified tissue, especially applicable to cell surface marker demonstration. J Histochem Cytochem 1988, 36:111-114
    • 32. Murakami T, Yamamoto M, Yamamoto M, Ono K, Nishikawa M, Nagata N, Motoyoshi K, Akatsu T: Transforming growth factor-1 increases mRNA levels of osteoclastogenesis inhibitory factor in osteoblastic/stromal cells and inhibits the survival of murine osteoclast-like cells. Biochem Biophys Res Commun 1998, 252:747-752
    • 33. Ott S, Chesnut C: Calcitriol treatment is not effective in postmenopausal osteoporosis. Ann Intern Med 1989, 110:267-274
    • 34. Owens J, Gallagher A, Chambers T: Bone cells required for osteoclastic resorption but not for osteoclastic differentiation. Biochem Biophys Res Comm 1996, 222:225-229
    • 35. Reynolds JJ, Pavlovitch H, Balsan S: 1,25-dihydroxycholecalciferol increases bone resorption in thyroparathyroidectomized mice. Calcif Tissue 1976, 21:207-212
    • 36. Riggs B, Nelson K: Effect of long-term treatment with calcitriol on calcium absorption and mineral metabolism in postmenopausal osteoporosis. Clin Endocrinol Metab 1985, 61:457-461
    • 37. Roodman G: Advances in bone biology: The osteoclast. Endoc Rev 1996, 17:308-332
    • 38. Sminia T, Dijkstra C: The origin of osteoclasts: An immunohistochemical study on macrophages and osteoclasts in embryonic rat bone. Calcif Tissue Int 1986, 39:263-266
    • 39. Solari F, Flamant Y, Cherel Y, Wyers M, Jurdic P: The osteoclast generation: an in vitro and in vivo study with a genetically labelled avian monocytic cell line. J Cell Sci 1996, 109:1203-1213
    • 40. Suda T, Shinki T, Takahashi N: The role of vitamin D in bone and intestinal cell differentiation. Ann Rev Nutr 1990, 10:195-211
    • 41. Suda T, Takahashi N, Abe E: Role of vitamin D in bone resorption. J Cell Biochem 1992, 49:53-58
    • 42. Tanaka Y, DeLuca H: Bone mineral mobilization of 1,25 (OH)2 D3, a metabolite of vitamin D. Arch Biochem Biophys 1971, 146:574-583
    • 43. Tinkler S, Williams D, Johnson N: Osteoclast formation in response to intra peritoneal injection of 1a-hydroxycholecalciferal in mice. J Anat 1981, 133:91-97
    • 44. Udagawa N, Takahashi N, Akatsu T, Tanaka H, Sasaki T, Nishihara T, Koga T, Martin TJ, Suda T: Origin of osteoclasts: mature monocytes and macrophages are capable of differentiating into osteoclasts under a suitable microenvironment prepared by bone marrow-derived stromal cells. Proc Nat Acad Sci USA 1990, 87:7260-7264
    • 45. Uy H, Dallas M, Calland JW, Boyce BF, Mundy GR, Roodman GD: Use of an in vivo model to determine the effects of interleukin-1 on cells at different stages in the osteoclast lineage. J Bone Miner Res 1995, 10:295-301
    • 46. Vaes G: Cellular biology and biochemical mechanism of bone resorption. A review of recent developments on the formation, activation and mode of action of osteoclasts Clin Orthop Rel Res 1988, 231:239-271
    • 47. Zerwekh J, Sakhaee K, Pak C: Short-term 1,25-dihydroxyvitamin D3 administration raises serum osteocalcin in patients with postmenopausal osteoporosis. J Clin Endocrinol Metab 1985, 60:615-617
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