Skip to main content
Erschienen in: Journal of Bone and Mineral Metabolism 1/2011

01.01.2011 | Original Article

Modeled microgravity and hindlimb unloading sensitize osteoclast precursors to RANKL-mediated osteoclastogenesis

verfasst von: Ritu Saxena, George Pan, Erik D. Dohm, Jay M. McDonald

Erschienen in: Journal of Bone and Mineral Metabolism | Ausgabe 1/2011

Einloggen, um Zugang zu erhalten

Abstract

Mechanical forces are essential to maintain skeletal integrity, and microgravity exposure leads to bone loss. The underlying molecular mechanisms leading to the changes in osteoblasts and osteoclast differentiation and function remain to be fully elucidated. Because of the infrequency of spaceflights and payload constraints, establishing in vitro and in vivo systems that mimic microgravity conditions becomes necessary. We have established a simulated microgravity (modeled microgravity, MMG) system to study the changes induced in osteoclast precursors. We observed that MMG, on its own, was unable to induce osteoclastogenesis of osteoclast precursors; however, 24 h of MMG activates osteoclastogenesis-related signaling molecules ERK, p38, PLCγ2, and NFATc1. Receptor activator of NFkB ligand (RANKL) (with or without M-CSF) stimulation for 3–4 days in gravity of cells that had been exposed to MMG for 24 h enhanced the formation of very large tartrate-resistant acid phosphatase (TRAP)-positive multinucleated (>30 nuclei) osteoclasts accompanied by an upregulation of the osteoclast marker genes TRAP and cathepsin K. To validate the in vitro system, we studied the hindlimb unloading (HLU) system using BALB/c mice and observed a decrease in BMD of femurs and a loss of 3D microstructure of both cortical and trabecular bone as determined by micro-CT. There was a marked stimulation of osteoclastogenesis as determined by the total number of TRAP-positive multinucleated osteoclasts formed and also an increase in RANKL-stimulated osteoclastogenesis from precursors removed from the tibias of mice after 28 days of HLU. In contrast to earlier reported findings, we did not observe any histomorphometric changes in the bone formation parameters. Thus, the foregoing observations indicate that microgravity sensitizes osteoclast precursors for increased differentiation. The in vitro model system described here is potentially a valid system for testing drugs for preventing microgravity-induced bone loss by targeting the molecular events occurring in microgravity-induced enhanced osteoclastogenesis.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Blanc S, Normand S, Ritz P, Pachiaudi C, Vico L, Gharib C, Gauquelin-Koch G (1998) Energy and water metabolism, body composition, and hormonal changes induced by 42 days of enforced inactivity and simulated weightlessness. J Clin Endocrinol Metab 83:4289–4297CrossRefPubMed Blanc S, Normand S, Ritz P, Pachiaudi C, Vico L, Gharib C, Gauquelin-Koch G (1998) Energy and water metabolism, body composition, and hormonal changes induced by 42 days of enforced inactivity and simulated weightlessness. J Clin Endocrinol Metab 83:4289–4297CrossRefPubMed
2.
Zurück zum Zitat Fowler JF Jr (1991) Physiological changes during spaceflight. Cutis 48:291–295PubMed Fowler JF Jr (1991) Physiological changes during spaceflight. Cutis 48:291–295PubMed
4.
Zurück zum Zitat Collet P, Uebelhart D, Vico L, Moro L, Hartmann D, Roth M, Alexandre C (1997) Effects of 1- and 6-month spaceflight on bone mass and biochemistry in two humans. Bone (NY) 20:547–551 Collet P, Uebelhart D, Vico L, Moro L, Hartmann D, Roth M, Alexandre C (1997) Effects of 1- and 6-month spaceflight on bone mass and biochemistry in two humans. Bone (NY) 20:547–551
5.
Zurück zum Zitat Lang T, LeBlanc A, Evans H, Lu Y, Genant H, Yu A (2004) Cortical and trabecular bone mineral loss from the spine and hip in long-duration spaceflight. J Bone Miner Res 19:1006–1012CrossRefPubMed Lang T, LeBlanc A, Evans H, Lu Y, Genant H, Yu A (2004) Cortical and trabecular bone mineral loss from the spine and hip in long-duration spaceflight. J Bone Miner Res 19:1006–1012CrossRefPubMed
6.
Zurück zum Zitat Vico L, Lafage-Proust MH, Alexandre C (1998) Effects of gravitational changes on the bone system in vitro and in vivo. Bone (NY) 22:95S–100S Vico L, Lafage-Proust MH, Alexandre C (1998) Effects of gravitational changes on the bone system in vitro and in vivo. Bone (NY) 22:95S–100S
7.
Zurück zum Zitat Caillot-Augusseau A, Lafage-Proust MH, Soler C, Pernod J, Dubois F, Alexandre C (1998) Bone formation and resorption biological markers in cosmonauts during and after a 180-day space flight (Euromir 95). Clin Chem 44:578–585PubMed Caillot-Augusseau A, Lafage-Proust MH, Soler C, Pernod J, Dubois F, Alexandre C (1998) Bone formation and resorption biological markers in cosmonauts during and after a 180-day space flight (Euromir 95). Clin Chem 44:578–585PubMed
8.
Zurück zum Zitat Smith SM, Nillen JL, Leblanc A, Lipton A, Demers LM, Lane HW, Leach CS (1998) Collagen cross-link excretion during space flight and bed rest. J Clin Endocrinol Metab 83:3584–3591CrossRefPubMed Smith SM, Nillen JL, Leblanc A, Lipton A, Demers LM, Lane HW, Leach CS (1998) Collagen cross-link excretion during space flight and bed rest. J Clin Endocrinol Metab 83:3584–3591CrossRefPubMed
9.
Zurück zum Zitat Smith SM, Wastney ME, O’Brien KO, Morukov BV, Larina IM, Abrams SA, Davis-Street JE, Oganov V, Shackelford LC (2005) Bone markers, calcium metabolism, and calcium kinetics during extended-duration space flight on the mir space station. J Bone Miner Res 20:208–218CrossRefPubMed Smith SM, Wastney ME, O’Brien KO, Morukov BV, Larina IM, Abrams SA, Davis-Street JE, Oganov V, Shackelford LC (2005) Bone markers, calcium metabolism, and calcium kinetics during extended-duration space flight on the mir space station. J Bone Miner Res 20:208–218CrossRefPubMed
10.
Zurück zum Zitat Abram AC, Keller TS, Spengler DM (1988) The effects of simulated weightlessness on bone biomechanical and biochemical properties in the maturing rat. J Biomech 21:755–767CrossRefPubMed Abram AC, Keller TS, Spengler DM (1988) The effects of simulated weightlessness on bone biomechanical and biochemical properties in the maturing rat. J Biomech 21:755–767CrossRefPubMed
11.
Zurück zum Zitat Vico L, Chappard D, Alexandre C, Palle S, Minaire P, Riffat G, Novikov VE, Bakulin AV (1987) Effects of weightlessness on bone mass and osteoclast number in pregnant rats after a five-day spaceflight (COSMOS 1514). Bone (NY) 8:95–103 Vico L, Chappard D, Alexandre C, Palle S, Minaire P, Riffat G, Novikov VE, Bakulin AV (1987) Effects of weightlessness on bone mass and osteoclast number in pregnant rats after a five-day spaceflight (COSMOS 1514). Bone (NY) 8:95–103
12.
Zurück zum Zitat Wronski TJ, Morey ER (1982) Skeletal abnormalities in rats induced by simulated weightlessness. Metab Bone Dis Relat Res 4:69–75CrossRefPubMed Wronski TJ, Morey ER (1982) Skeletal abnormalities in rats induced by simulated weightlessness. Metab Bone Dis Relat Res 4:69–75CrossRefPubMed
13.
Zurück zum Zitat Morey ER, Baylink DJ (1978) Inhibition of bone formation during space flight. Science 201:1138–1141CrossRefPubMed Morey ER, Baylink DJ (1978) Inhibition of bone formation during space flight. Science 201:1138–1141CrossRefPubMed
14.
Zurück zum Zitat Spengler DM, Morey ER, Carter DR, Turner RT, Baylink DJ (1983) Effects of spaceflight on structural and material strength of growing bone. Proc Soc Exp Biol Med 174:224–228PubMed Spengler DM, Morey ER, Carter DR, Turner RT, Baylink DJ (1983) Effects of spaceflight on structural and material strength of growing bone. Proc Soc Exp Biol Med 174:224–228PubMed
15.
Zurück zum Zitat Turner RT, Wakley GK, Szukalski BW (1985) Effects of gravitational and muscular loading on bone formation in growing rats. Physiologist 28:S67–S68PubMed Turner RT, Wakley GK, Szukalski BW (1985) Effects of gravitational and muscular loading on bone formation in growing rats. Physiologist 28:S67–S68PubMed
16.
Zurück zum Zitat Wronski TJ, Morey ER (1983) Recovery of the rat skeleton from the adverse effects of simulated weightlessness. Metab Bone Dis Relat Res 4:347–352PubMed Wronski TJ, Morey ER (1983) Recovery of the rat skeleton from the adverse effects of simulated weightlessness. Metab Bone Dis Relat Res 4:347–352PubMed
17.
Zurück zum Zitat Davis BA, Sipe B, Gershan LA, Fiacco GJ, Lorenz TC, Jeffrey JJ, Partridge NC (1998) Collagenase and tissue plasminogen activator production in developing rat calvariae: normal progression despite fetal exposure to microgravity. Calcif Tissue Int 63:416–422CrossRefPubMed Davis BA, Sipe B, Gershan LA, Fiacco GJ, Lorenz TC, Jeffrey JJ, Partridge NC (1998) Collagenase and tissue plasminogen activator production in developing rat calvariae: normal progression despite fetal exposure to microgravity. Calcif Tissue Int 63:416–422CrossRefPubMed
18.
Zurück zum Zitat Vico L, Bourrin S, Genty C, Palle S, Alexandre C (1993) Histomorphometric analyses of cancellous bone from COSMOS 2044 rats. J Appl Physiol 75:2203–2208PubMed Vico L, Bourrin S, Genty C, Palle S, Alexandre C (1993) Histomorphometric analyses of cancellous bone from COSMOS 2044 rats. J Appl Physiol 75:2203–2208PubMed
19.
Zurück zum Zitat Kaplansky AS, Durnova GN, Burkovskaya TE, Vorotnikova EV (1991) The effect of microgravity on bone fracture healing in rats flown on Cosmos-2044. Physiologist 34:S196–S199PubMed Kaplansky AS, Durnova GN, Burkovskaya TE, Vorotnikova EV (1991) The effect of microgravity on bone fracture healing in rats flown on Cosmos-2044. Physiologist 34:S196–S199PubMed
20.
Zurück zum Zitat Wronski TJ, Morey ER (1983) Alterations in calcium homeostasis and bone during actual and simulated space flight. Med Sci Sports Exerc 15:410–414PubMed Wronski TJ, Morey ER (1983) Alterations in calcium homeostasis and bone during actual and simulated space flight. Med Sci Sports Exerc 15:410–414PubMed
21.
Zurück zum Zitat Van Loon JJ, Bervoets DJ, Burger EH, Dieudonné SC, Hagen JW, Semeins CM, Doulabi BZ, Veldhuijzen JP (1995) Decreased mineralization and increased calcium release in isolated fetal mouse long bones under near weightlessness. J Bone Miner Res 10:550–557CrossRefPubMed Van Loon JJ, Bervoets DJ, Burger EH, Dieudonné SC, Hagen JW, Semeins CM, Doulabi BZ, Veldhuijzen JP (1995) Decreased mineralization and increased calcium release in isolated fetal mouse long bones under near weightlessness. J Bone Miner Res 10:550–557CrossRefPubMed
22.
Zurück zum Zitat Berezovska OP, Rodionova NV, Grigoryan EN, Mitashov VI (1998) Changes in the numbers of osteoclasts in newts under conditions of microgravity. Adv Space Res 21:1059–1063CrossRefPubMed Berezovska OP, Rodionova NV, Grigoryan EN, Mitashov VI (1998) Changes in the numbers of osteoclasts in newts under conditions of microgravity. Adv Space Res 21:1059–1063CrossRefPubMed
23.
Zurück zum Zitat Zerath E, Holy X, Andre C, Renault S, Noel B, Delannoy P, Hott M, Marie PJ (2000) Effects of Bion 11 14-day space flight on monkey iliac bone. J Gravit Physiol 7:S155–S156PubMed Zerath E, Holy X, Andre C, Renault S, Noel B, Delannoy P, Hott M, Marie PJ (2000) Effects of Bion 11 14-day space flight on monkey iliac bone. J Gravit Physiol 7:S155–S156PubMed
24.
Zurück zum Zitat Scheld K, Zittermann A, Heer M, Herzog B, Mika C, Drummer C, Stehle P (2001) Nitrogen metabolism and bone metabolism markers in healthy adults during 16 weeks of bed rest. Clin Chem 47:1688–1695PubMed Scheld K, Zittermann A, Heer M, Herzog B, Mika C, Drummer C, Stehle P (2001) Nitrogen metabolism and bone metabolism markers in healthy adults during 16 weeks of bed rest. Clin Chem 47:1688–1695PubMed
25.
Zurück zum Zitat Morey-Holton ER, Globus RK (1998) Hindlimb unloading of growing rats: a model for predicting skeletal changes during space flight. Bone 22:83S–88SCrossRefPubMed Morey-Holton ER, Globus RK (1998) Hindlimb unloading of growing rats: a model for predicting skeletal changes during space flight. Bone 22:83S–88SCrossRefPubMed
26.
Zurück zum Zitat Globus RK, Bikle DD, Morey-Holton E (1984) Effects of simulated weightlessness on bone mineral metabolism. Endocrinology 114:2264–2270CrossRefPubMed Globus RK, Bikle DD, Morey-Holton E (1984) Effects of simulated weightlessness on bone mineral metabolism. Endocrinology 114:2264–2270CrossRefPubMed
27.
Zurück zum Zitat Halloran BP, Bikle DD, Cone CM, Morey-Holton E (1988) Glucocorticoids and inhibition of bone formation induced by skeletal unloading. Am J Physiol 255:E875–E879PubMed Halloran BP, Bikle DD, Cone CM, Morey-Holton E (1988) Glucocorticoids and inhibition of bone formation induced by skeletal unloading. Am J Physiol 255:E875–E879PubMed
28.
Zurück zum Zitat Simske SJ, Guerra KM, Greenberg AR, Luttges MW (1992) The physical and mechanical effects of suspension-induced osteopenia on mouse long bones. J Biomech 25:489–499CrossRefPubMed Simske SJ, Guerra KM, Greenberg AR, Luttges MW (1992) The physical and mechanical effects of suspension-induced osteopenia on mouse long bones. J Biomech 25:489–499CrossRefPubMed
29.
Zurück zum Zitat Sakata T, Sakai A, Tsurukami H, Okimoto N, Okazaki Y, Ikeda S, Norimura T, Nakamura T (1999) Trabecular bone turnover and bone marrow cell development in tail-suspended mice. J Bone Miner Res 14:1596–1604CrossRefPubMed Sakata T, Sakai A, Tsurukami H, Okimoto N, Okazaki Y, Ikeda S, Norimura T, Nakamura T (1999) Trabecular bone turnover and bone marrow cell development in tail-suspended mice. J Bone Miner Res 14:1596–1604CrossRefPubMed
30.
Zurück zum Zitat Saxena R, Pan G, McDonald JM (2007) Osteoblast and osteoclast differentiation in modeled microgravity. Ann N Y Acad Sci 1116:494–4988CrossRefPubMed Saxena R, Pan G, McDonald JM (2007) Osteoblast and osteoclast differentiation in modeled microgravity. Ann N Y Acad Sci 1116:494–4988CrossRefPubMed
31.
Zurück zum Zitat Hammond TG, Hammond JM (2001) Optimized suspension culture: the rotating-wall vessel. Am J Physiol Renal Physiol 281:F12–F25PubMed Hammond TG, Hammond JM (2001) Optimized suspension culture: the rotating-wall vessel. Am J Physiol Renal Physiol 281:F12–F25PubMed
32.
Zurück zum Zitat Sarkar D, Nagaya T, Koga K, Kambe F, Nomura Y, Seo H (2000) Rotation in clinostat results in apoptosis of osteoblastic ROS 17/2.8 cells. J Gravit Physiol 7:P71–P72PubMed Sarkar D, Nagaya T, Koga K, Kambe F, Nomura Y, Seo H (2000) Rotation in clinostat results in apoptosis of osteoblastic ROS 17/2.8 cells. J Gravit Physiol 7:P71–P72PubMed
33.
Zurück zum Zitat Kanematsu M, Yoshimura K, Takaoki M, Sato A (2002) Vector-averaged gravity regulates gene expression of receptor activator of NF-kappaB (RANK) ligand and osteoprotegerin in bone marrow stromal cells via cyclic AMP/protein kinase A pathway. Bone (NY) 30:553–558 Kanematsu M, Yoshimura K, Takaoki M, Sato A (2002) Vector-averaged gravity regulates gene expression of receptor activator of NF-kappaB (RANK) ligand and osteoprotegerin in bone marrow stromal cells via cyclic AMP/protein kinase A pathway. Bone (NY) 30:553–558
34.
Zurück zum Zitat Rucci N, Rufo A, Alamanou M, Teti (2007) Modeled microgravity stimulates osteoclastogenesis and bone resorption by increasing osteoblast RANKL/OPG ratio. J Cell Biochem 100:464–473CrossRefPubMed Rucci N, Rufo A, Alamanou M, Teti (2007) Modeled microgravity stimulates osteoclastogenesis and bone resorption by increasing osteoblast RANKL/OPG ratio. J Cell Biochem 100:464–473CrossRefPubMed
35.
Zurück zum Zitat Bikle DD, Morey-Holton ER, Doty SB, Currier PA, Tanner SJ, Halloran BP (1994) Alendronate increases skeletal mass of growing rats during unloading by inhibiting resorption of calcified cartilage. J Bone Miner Res 9:1777–1787CrossRefPubMed Bikle DD, Morey-Holton ER, Doty SB, Currier PA, Tanner SJ, Halloran BP (1994) Alendronate increases skeletal mass of growing rats during unloading by inhibiting resorption of calcified cartilage. J Bone Miner Res 9:1777–1787CrossRefPubMed
36.
Zurück zum Zitat Machwate M, Zerath E, Holy X, Hott M, Modrowski D, Malouvier A, Marie PJ (1993) Skeletal unloading in rat decreases proliferation of rat bone and marrow-derived osteoblastic cells. Am J Physiol 264:E790–E799PubMed Machwate M, Zerath E, Holy X, Hott M, Modrowski D, Malouvier A, Marie PJ (1993) Skeletal unloading in rat decreases proliferation of rat bone and marrow-derived osteoblastic cells. Am J Physiol 264:E790–E799PubMed
37.
Zurück zum Zitat Machwate M, Zerath E, Holy X, Pastoureau P, Marie PJ (1994) Insulin-like growth factor-I increases trabecular bone formation and osteoblastic cell proliferation in unloaded rats. Endocrinology 134:1031–1038CrossRefPubMed Machwate M, Zerath E, Holy X, Pastoureau P, Marie PJ (1994) Insulin-like growth factor-I increases trabecular bone formation and osteoblastic cell proliferation in unloaded rats. Endocrinology 134:1031–1038CrossRefPubMed
38.
Zurück zum Zitat Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ et al (1987) Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res 2:595–610CrossRefPubMed Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ et al (1987) Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res 2:595–610CrossRefPubMed
39.
Zurück zum Zitat Meyers VE, Zayzafoon M, Douglas JT, McDonald JM (2005) RhoA and cytoskeletal disruption mediate reduced osteoblastogenesis and enhanced adipogenesis of human mesenchymal stem cells in modeled microgravity. J Bone Miner Res 20:1858–1866CrossRefPubMed Meyers VE, Zayzafoon M, Douglas JT, McDonald JM (2005) RhoA and cytoskeletal disruption mediate reduced osteoblastogenesis and enhanced adipogenesis of human mesenchymal stem cells in modeled microgravity. J Bone Miner Res 20:1858–1866CrossRefPubMed
40.
Zurück zum Zitat Zayzafoon M, Gathings WE, McDonald JM (2004) Modeled microgravity inhibits osteogenic differentiation of human mesenchymal stem cells and increases adipogenesis. Endocrinology 145:2421–2432CrossRefPubMed Zayzafoon M, Gathings WE, McDonald JM (2004) Modeled microgravity inhibits osteogenic differentiation of human mesenchymal stem cells and increases adipogenesis. Endocrinology 145:2421–2432CrossRefPubMed
41.
Zurück zum Zitat Meyers VE, Zayzafoon M, Gonda SR, Gathings WE, McDonald JM (2004) Modeled microgravity disrupts collagen I/integrin signaling during osteoblastic differentiation of human mesenchymal stem cells. Cell Biochem 93:697–707CrossRef Meyers VE, Zayzafoon M, Gonda SR, Gathings WE, McDonald JM (2004) Modeled microgravity disrupts collagen I/integrin signaling during osteoblastic differentiation of human mesenchymal stem cells. Cell Biochem 93:697–707CrossRef
42.
Zurück zum Zitat Zayzafoon M, Meyers VE, McDonald JM (2005) Microgravity: the immune response and bone. Immunol Rev 208:267–280CrossRefPubMed Zayzafoon M, Meyers VE, McDonald JM (2005) Microgravity: the immune response and bone. Immunol Rev 208:267–280CrossRefPubMed
43.
Zurück zum Zitat Hirotani H, Tuohy NA, Woo JT, Stern PH, Clipstone NA (2004) The calcineurin/nuclear factor of activated T cells signaling pathway regulates osteoclastogenesis in RAW264.7 cells. J Biol Chem 279:13984–13992CrossRefPubMed Hirotani H, Tuohy NA, Woo JT, Stern PH, Clipstone NA (2004) The calcineurin/nuclear factor of activated T cells signaling pathway regulates osteoclastogenesis in RAW264.7 cells. J Biol Chem 279:13984–13992CrossRefPubMed
44.
Zurück zum Zitat Matsuo K, Galson DL, Zhao C, Peng L, Laplace C, Wang KZ, Bachler MA, Amano H, Aburatani H, Ishikawa H, Wagner EF (2004) Nuclear factor of activated T-cells (NFAT) rescues osteoclastogenesis in precursors lacking c-Fos. J Biol Chem 279:26475–26480CrossRefPubMed Matsuo K, Galson DL, Zhao C, Peng L, Laplace C, Wang KZ, Bachler MA, Amano H, Aburatani H, Ishikawa H, Wagner EF (2004) Nuclear factor of activated T-cells (NFAT) rescues osteoclastogenesis in precursors lacking c-Fos. J Biol Chem 279:26475–26480CrossRefPubMed
45.
46.
Zurück zum Zitat Tamma R, Colaianni G, Camerino C, Di Benedetto A, Greco G, Strippoli M, Vergari R, Grano A, Mancini L, Mori G, Colucci S, Grano M, Zallone A (2009) Microgravity during spaceflight directly affects in vitro osteoclastogenesis and bone resorption. FASEB J 23:2549–2554CrossRefPubMed Tamma R, Colaianni G, Camerino C, Di Benedetto A, Greco G, Strippoli M, Vergari R, Grano A, Mancini L, Mori G, Colucci S, Grano M, Zallone A (2009) Microgravity during spaceflight directly affects in vitro osteoclastogenesis and bone resorption. FASEB J 23:2549–2554CrossRefPubMed
47.
Zurück zum Zitat Monici M, Fusi F, Paglierani M, Marziliano N, Cogoli A, Pratesi R, Bernabei PA (2006) Modeled gravitational unloading triggers differentiation and apoptosis in preosteoclastic cells. J Cell Biochem 98:65–80CrossRefPubMed Monici M, Fusi F, Paglierani M, Marziliano N, Cogoli A, Pratesi R, Bernabei PA (2006) Modeled gravitational unloading triggers differentiation and apoptosis in preosteoclastic cells. J Cell Biochem 98:65–80CrossRefPubMed
48.
Zurück zum Zitat Monici M, Agati G, Fusi F, Paglierani M, Cogoli A, Bernabei PA (2002) Gravitational unloading induces osteoclast-like differentiation of FLG 29.1 cells. J Gravit Physiol 9:261–262 Monici M, Agati G, Fusi F, Paglierani M, Cogoli A, Bernabei PA (2002) Gravitational unloading induces osteoclast-like differentiation of FLG 29.1 cells. J Gravit Physiol 9:261–262
49.
Zurück zum Zitat Seales EC, Micoli KJ, McDonald JM (2006) Calmodulin is a critical regulator of osteoclastic differentiation, function, and survival. J Cell Biochem 97:45–55CrossRefPubMed Seales EC, Micoli KJ, McDonald JM (2006) Calmodulin is a critical regulator of osteoclastic differentiation, function, and survival. J Cell Biochem 97:45–55CrossRefPubMed
50.
Zurück zum Zitat Zayzafoon M, Fulzele K, McDonald JM (2005) Calmodulin and calmodulin-dependent kinase IIalpha regulate osteoblast differentiation by controlling c-fos expression. J Biol Chem 280:7049–7059CrossRefPubMed Zayzafoon M, Fulzele K, McDonald JM (2005) Calmodulin and calmodulin-dependent kinase IIalpha regulate osteoblast differentiation by controlling c-fos expression. J Biol Chem 280:7049–7059CrossRefPubMed
51.
Zurück zum Zitat Yeo H, Beck LH, McDonald JM, Zayzafoon M (2007) Cyclosporin A elicits dose-dependent biphasic effects on osteoblast differentiation and bone formation. Bone (NY) 40:1502–1516 Yeo H, Beck LH, McDonald JM, Zayzafoon M (2007) Cyclosporin A elicits dose-dependent biphasic effects on osteoblast differentiation and bone formation. Bone (NY) 40:1502–1516
52.
Zurück zum Zitat Aguirre JI, Plotkin LI, Stewart SA, Weinstein RS, Parfitt AM, Manolagas SC, Bellido T (2006) Osteocyte apoptosis is induced by weightlessness in mice and precedes osteoclast recruitment and bone loss. J Bone Miner Res 21:605–615CrossRefPubMed Aguirre JI, Plotkin LI, Stewart SA, Weinstein RS, Parfitt AM, Manolagas SC, Bellido T (2006) Osteocyte apoptosis is induced by weightlessness in mice and precedes osteoclast recruitment and bone loss. J Bone Miner Res 21:605–615CrossRefPubMed
53.
Zurück zum Zitat Matsumoto T, Nakayama K, Kodama Y, Fuse H, Nakamura T, Fukumoto S (1998) Effect of mechanical unloading and reloading on periosteal bone formation and gene expression in tail-suspended rapidly growing rats. Bone (NY) 22:89S–93S Matsumoto T, Nakayama K, Kodama Y, Fuse H, Nakamura T, Fukumoto S (1998) Effect of mechanical unloading and reloading on periosteal bone formation and gene expression in tail-suspended rapidly growing rats. Bone (NY) 22:89S–93S
54.
Zurück zum Zitat Hefferan TE, Evans GL, Lotinun S, Zhang M, Morey-Holton E, Turner RT (2003) Effect of gender on bone turnover in adult rats during simulated weightlessness. J Appl Physiol 95:1775–1780PubMed Hefferan TE, Evans GL, Lotinun S, Zhang M, Morey-Holton E, Turner RT (2003) Effect of gender on bone turnover in adult rats during simulated weightlessness. J Appl Physiol 95:1775–1780PubMed
55.
Zurück zum Zitat Dehority W, Halloran BP, Bikle DD, Curren T, Kostenuik PJ, Wronski TJ, Shen Y, Rabkin B, Bouraoui A, Morey-Holton E (1999) Bone and hormonal changes induced by skeletal unloading in the mature male rat. Am J Physiol 276:E62–E69PubMed Dehority W, Halloran BP, Bikle DD, Curren T, Kostenuik PJ, Wronski TJ, Shen Y, Rabkin B, Bouraoui A, Morey-Holton E (1999) Bone and hormonal changes induced by skeletal unloading in the mature male rat. Am J Physiol 276:E62–E69PubMed
56.
Zurück zum Zitat Huang DW, Wan YM, Shi ZZ, Huang ZM, Li YH, Ma YJ (2003) Effects of hindlimb unloading on bone histomorphometry and bone mass in rats (in Chinese). Space Med Med Eng (Beijing) 16:418–421 Huang DW, Wan YM, Shi ZZ, Huang ZM, Li YH, Ma YJ (2003) Effects of hindlimb unloading on bone histomorphometry and bone mass in rats (in Chinese). Space Med Med Eng (Beijing) 16:418–421
57.
Zurück zum Zitat Li XJ, Jee WS, Chow SY, Woodbury DM (1990) Adaptation of cancellous bone to aging and immobilization in the rat: a single photon absorptiometry and histomorphometry study. Anat Rec 227:12–24CrossRefPubMed Li XJ, Jee WS, Chow SY, Woodbury DM (1990) Adaptation of cancellous bone to aging and immobilization in the rat: a single photon absorptiometry and histomorphometry study. Anat Rec 227:12–24CrossRefPubMed
58.
Zurück zum Zitat Lloyd SA, Travis ND, Lu T, Bateman TA (2008) Development of a low-dose anti-resorptive drug regimen reveals synergistic suppression of bone formation when coupled with disuse. J Appl Physiol 104:729–738CrossRefPubMed Lloyd SA, Travis ND, Lu T, Bateman TA (2008) Development of a low-dose anti-resorptive drug regimen reveals synergistic suppression of bone formation when coupled with disuse. J Appl Physiol 104:729–738CrossRefPubMed
59.
Zurück zum Zitat Turner RT, Evans GL, Lotinun S, Lapke PD, Iwaniec UT, Morey-Holton E (2007) Dose-response effects of intermittent PTH on cancellous bone in hindlimb unloaded rats. J Bone Miner Res 22:64–71CrossRefPubMed Turner RT, Evans GL, Lotinun S, Lapke PD, Iwaniec UT, Morey-Holton E (2007) Dose-response effects of intermittent PTH on cancellous bone in hindlimb unloaded rats. J Bone Miner Res 22:64–71CrossRefPubMed
60.
Zurück zum Zitat Locklin RM, Khosla S, Turner RT, Riggs BL (2003) Mediators of the biphasic responses of bone to intermittent and continuously administered parathyroid hormone. J Cell Biochem 89:180–190CrossRefPubMed Locklin RM, Khosla S, Turner RT, Riggs BL (2003) Mediators of the biphasic responses of bone to intermittent and continuously administered parathyroid hormone. J Cell Biochem 89:180–190CrossRefPubMed
61.
Zurück zum Zitat Hock JM, Gera I (1992) Effects of continuous and intermittent administration and inhibition of resorption on the anabolic response of bone to parathyroid hormone. J Bone Miner Res 7:65–72CrossRefPubMed Hock JM, Gera I (1992) Effects of continuous and intermittent administration and inhibition of resorption on the anabolic response of bone to parathyroid hormone. J Bone Miner Res 7:65–72CrossRefPubMed
62.
Zurück zum Zitat Ono N, Nakashima K, Schipani E, Hayata T, Ezura Y, Soma K, Kronenberg HM, Noda M (2007) Constitutively active parathyroid hormone receptor signaling in cells in osteoblastic lineage suppresses mechanical unloading-induced bone resorption. J Biol Chem 282:25509–25516CrossRefPubMed Ono N, Nakashima K, Schipani E, Hayata T, Ezura Y, Soma K, Kronenberg HM, Noda M (2007) Constitutively active parathyroid hormone receptor signaling in cells in osteoblastic lineage suppresses mechanical unloading-induced bone resorption. J Biol Chem 282:25509–25516CrossRefPubMed
63.
Zurück zum Zitat Baek K, Bloomfield SA (2009) Beta-adrenergic blockade and leptin replacement effectively mitigate disuse bone loss. J Bone Miner Res 24:792–799CrossRefPubMed Baek K, Bloomfield SA (2009) Beta-adrenergic blockade and leptin replacement effectively mitigate disuse bone loss. J Bone Miner Res 24:792–799CrossRefPubMed
64.
Zurück zum Zitat Lin C, Jiang X, Dai Z, Guo X, Weng T, Wang J, Li Y, Feng G, Gao X, He L (2009) Sclerostin mediates bone response to mechanical unloading via antagonizing Wnt/beta-catenin signaling. J Bone Miner Res 24:1651–1661CrossRefPubMed Lin C, Jiang X, Dai Z, Guo X, Weng T, Wang J, Li Y, Feng G, Gao X, He L (2009) Sclerostin mediates bone response to mechanical unloading via antagonizing Wnt/beta-catenin signaling. J Bone Miner Res 24:1651–1661CrossRefPubMed
Metadaten
Titel
Modeled microgravity and hindlimb unloading sensitize osteoclast precursors to RANKL-mediated osteoclastogenesis
verfasst von
Ritu Saxena
George Pan
Erik D. Dohm
Jay M. McDonald
Publikationsdatum
01.01.2011
Verlag
Springer Japan
Erschienen in
Journal of Bone and Mineral Metabolism / Ausgabe 1/2011
Print ISSN: 0914-8779
Elektronische ISSN: 1435-5604
DOI
https://doi.org/10.1007/s00774-010-0201-4

Weitere Artikel der Ausgabe 1/2011

Journal of Bone and Mineral Metabolism 1/2011 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Reizdarmsyndrom: Diäten wirksamer als Medikamente

29.04.2024 Reizdarmsyndrom Nachrichten

Bei Reizdarmsyndrom scheinen Diäten, wie etwa die FODMAP-arme oder die kohlenhydratreduzierte Ernährung, effektiver als eine medikamentöse Therapie zu sein. Das hat eine Studie aus Schweden ergeben, die die drei Therapieoptionen im direkten Vergleich analysierte.

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.