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Published in: Calcified Tissue International 4/2011

01-04-2011 | Original Research

Osteoblast Response to Ovariectomy Is Enhanced in Intrinsically High Aerobic-Capacity Rats

Authors: G. C. Goulet, N. R. Halonen, L. G. Koch, S. L. Britton, R. F. Zernicke, K. M. Kozloff

Published in: Calcified Tissue International | Issue 4/2011

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Abstract

The role of exercise in promoting bone health is typically attributed to increased mechanical loading, which induces functional adaptation. Recent evidence suggests that habitual aerobic exercise has influence at the cellular level as well. The effect of aerobic capacity on osteoblast-lineage cell differentiation and function as well as skeletal phenotype is unknown. Using a rat model of high-capacity and low-capacity runners (HCRs and LCRs, respectively), in which an intrinsic functional genomic difference in aerobic capacity exists between nontrained animals, this study evaluated the effects of aerobic capacity on measures of bone mass and strength as well as osteoblast activity following ovariectomy. The ovariectomized rat emulates the clinical features of the estrogen-depleted human skeleton and represents a valuable model for studying short-term upregulation of osteoblast activity. We hypothesized that intrinsically high aerobic capacity would augment osteoblast response, which would mitigate the deleterious effects of hormone withdrawal. Femora and tibiae were assessed by micro-computed tomography, mechanical testing, and dynamic histomorphometry. HCRs had enhanced femoral tissue mineral density and estimated elastic modulus relative to LCRs. At 4 weeks postovariectomy, HCRs demonstrated a more robust osteoblast response. Markers of bone formation were upregulated to a greater extent in HCRs than LCRs, suggesting a role for aerobic capacity in governing osteoblast activity. Results from this and future studies will help to identify the influence of cellular aerobic metabolism on bone health, which may lead to new strategies for targeting diseases of the skeleton.
Literature
1.
go back to reference Davies KJ, Packer L, Brooks GA (1981) Biochemical adaptation of mitochondria, muscle, and whole-animal respiration to endurance training. Arch Biochem Biophys 209:539–554PubMedCrossRef Davies KJ, Packer L, Brooks GA (1981) Biochemical adaptation of mitochondria, muscle, and whole-animal respiration to endurance training. Arch Biochem Biophys 209:539–554PubMedCrossRef
2.
go back to reference Navarro A, Gomez C, Lopez-Cepero JM, Boveris A (2004) Beneficial effects of moderate exercise on mice aging: survival, behavior, oxidative stress, and mitochondrial electron transfer. Am J Physiol Regul Integr Comp Physiol 286:R505–R511PubMedCrossRef Navarro A, Gomez C, Lopez-Cepero JM, Boveris A (2004) Beneficial effects of moderate exercise on mice aging: survival, behavior, oxidative stress, and mitochondrial electron transfer. Am J Physiol Regul Integr Comp Physiol 286:R505–R511PubMedCrossRef
3.
go back to reference Boveris A, Navarro A (2008) Systemic and mitochondrial adaptive responses to moderate exercise in rodents. Free Radic Biol Med 44:224–229PubMedCrossRef Boveris A, Navarro A (2008) Systemic and mitochondrial adaptive responses to moderate exercise in rodents. Free Radic Biol Med 44:224–229PubMedCrossRef
4.
go back to reference Koch LG, Britton SL (2001) Artificial selection for intrinsic aerobic endurance running capacity in rats. Physiol Genomics 5:45–52PubMed Koch LG, Britton SL (2001) Artificial selection for intrinsic aerobic endurance running capacity in rats. Physiol Genomics 5:45–52PubMed
5.
go back to reference Wisloff U, Najjar SM, Ellingsen O, Haram PM, Swoap S, Al-Share Q, Fernstrom M, Rezaei K, Lee SJ, Koch LG, Britton SL (2005) Cardiovascular risk factors emerge after artificial selection for low aerobic capacity. Science 307:418–420PubMedCrossRef Wisloff U, Najjar SM, Ellingsen O, Haram PM, Swoap S, Al-Share Q, Fernstrom M, Rezaei K, Lee SJ, Koch LG, Britton SL (2005) Cardiovascular risk factors emerge after artificial selection for low aerobic capacity. Science 307:418–420PubMedCrossRef
6.
go back to reference Noland RC, Thyfault JP, Henes ST, Whitfield BR, Woodlief TL, Evans JR, Lust JA, Britton SL, Koch LG, Dudek RW, Dohm GL, Cortright RN, Lust RM (2007) Artificial selection for high-capacity endurance running is protective against high-fat diet-induced insulin resistance. Am J Physiol Endocrinol Metab 293:E31–E41PubMedCrossRef Noland RC, Thyfault JP, Henes ST, Whitfield BR, Woodlief TL, Evans JR, Lust JA, Britton SL, Koch LG, Dudek RW, Dohm GL, Cortright RN, Lust RM (2007) Artificial selection for high-capacity endurance running is protective against high-fat diet-induced insulin resistance. Am J Physiol Endocrinol Metab 293:E31–E41PubMedCrossRef
7.
go back to reference Morris EM, Whaley-Connell AT, Thyfault JP, Britton SL, Koch LG, Wei Y, Ibdah JA, Sowers JR (2009) Low aerobic capacity and high-fat diet contribute to oxidative stress and IRS-1 degradation in the kidney. Am J Nephrol 30:112–119PubMedCrossRef Morris EM, Whaley-Connell AT, Thyfault JP, Britton SL, Koch LG, Wei Y, Ibdah JA, Sowers JR (2009) Low aerobic capacity and high-fat diet contribute to oxidative stress and IRS-1 degradation in the kidney. Am J Nephrol 30:112–119PubMedCrossRef
8.
go back to reference Hirao M, Hashimoto J, Yamasaki N, Ando W, Tsuboi H, Myoui A, Yoshikawa H (2007) Oxygen tension is an important mediator of the transformation of osteoblasts to osteocytes. J Bone Miner Metab 25:266–276PubMedCrossRef Hirao M, Hashimoto J, Yamasaki N, Ando W, Tsuboi H, Myoui A, Yoshikawa H (2007) Oxygen tension is an important mediator of the transformation of osteoblasts to osteocytes. J Bone Miner Metab 25:266–276PubMedCrossRef
9.
go back to reference Zahm AM, Bucaro MA, Srinivas V, Shapiro IM, Adams CS (2008) Oxygen tension regulates preosteocyte maturation and mineralization. Bone 43:25–31PubMedCrossRef Zahm AM, Bucaro MA, Srinivas V, Shapiro IM, Adams CS (2008) Oxygen tension regulates preosteocyte maturation and mineralization. Bone 43:25–31PubMedCrossRef
10.
go back to reference Halonen NR, Cole JH, Goulet GC, Sobel A, Koch LG, Britton SL, Morris MD, Zernicke RF, Kozloff K (2010) Influence of intrinsic and trained aerobic capacity on bone mineralization and material properties. In: Transactions of the 56th Annual Meeting of the Orthopaedic Research Society, New Orleans, LA, 35:0069 Halonen NR, Cole JH, Goulet GC, Sobel A, Koch LG, Britton SL, Morris MD, Zernicke RF, Kozloff K (2010) Influence of intrinsic and trained aerobic capacity on bone mineralization and material properties. In: Transactions of the 56th Annual Meeting of the Orthopaedic Research Society, New Orleans, LA, 35:0069
11.
go back to reference Halonen NR, Tayim R, Goulet GC, Cole JH, Clifford C, Goldstein SA, Koch LG, Britton SL, Zernicke RF, Alford AI, Kozloff K (2010) Intrinsic aerobic capacity influences MSC proliferation, mineralization, and fracture healing. In: Transactions of the 56th Annual Meeting of the Orthopaedic Research Society, New Orleans, LA, 35:1712 Halonen NR, Tayim R, Goulet GC, Cole JH, Clifford C, Goldstein SA, Koch LG, Britton SL, Zernicke RF, Alford AI, Kozloff K (2010) Intrinsic aerobic capacity influences MSC proliferation, mineralization, and fracture healing. In: Transactions of the 56th Annual Meeting of the Orthopaedic Research Society, New Orleans, LA, 35:1712
12.
go back to reference Jee WS, Yao W (2001) Overview: animal models of osteopenia and osteoporosis. J Musculoskelet Neuronal Interact 1:193–207PubMed Jee WS, Yao W (2001) Overview: animal models of osteopenia and osteoporosis. J Musculoskelet Neuronal Interact 1:193–207PubMed
13.
go back to reference Bagi CM, DeLeon E, Ammann P, Rizzoli R, Miller SC (1996) Histo-anatomy of the proximal femur in rats: impact of ovariectomy on bone mass, structure, and stiffness. Anat Rec 245:633–644PubMedCrossRef Bagi CM, DeLeon E, Ammann P, Rizzoli R, Miller SC (1996) Histo-anatomy of the proximal femur in rats: impact of ovariectomy on bone mass, structure, and stiffness. Anat Rec 245:633–644PubMedCrossRef
14.
go back to reference Sato M, Zeng GQ, Turner CH (1997) Biosynthetic human parathyroid hormone (1–34) effects on bone quality in aged ovariectomized rats. Endocrinology 138:4330–4337PubMedCrossRef Sato M, Zeng GQ, Turner CH (1997) Biosynthetic human parathyroid hormone (1–34) effects on bone quality in aged ovariectomized rats. Endocrinology 138:4330–4337PubMedCrossRef
15.
16.
go back to reference Taylor DK, Meganck JA, Terkhorn S, Rajani R, Naik A, O’Keefe RJ, Goldstein SA, Hankenson KD (2009) Thrombospondin-2 influences the proportion of cartilage and bone during fracture healing. J Bone Miner Res 24:1043–1054PubMedCrossRef Taylor DK, Meganck JA, Terkhorn S, Rajani R, Naik A, O’Keefe RJ, Goldstein SA, Hankenson KD (2009) Thrombospondin-2 influences the proportion of cartilage and bone during fracture healing. J Bone Miner Res 24:1043–1054PubMedCrossRef
17.
go back to reference Hou JC, Zernicke RF, Barnard RJ (1990) High fat–sucrose diet effects on femoral neck geometry and biomechanics. Clin Biomech (Bristol, Avon) 5:162–168CrossRef Hou JC, Zernicke RF, Barnard RJ (1990) High fat–sucrose diet effects on femoral neck geometry and biomechanics. Clin Biomech (Bristol, Avon) 5:162–168CrossRef
18.
go back to reference Manske SL, Steiner D, Kim SH, Boyd SK, Koch LG, Britton SL, Hepple RT, Zernicke RF (2008) Differences in bone morphology in older female rats selectively bred for high and low aerobic capacity. In: Transactions of the 54th Annual Meeting of the Orthopaedic Research Society, San Francisco, CA, 33:0910 Manske SL, Steiner D, Kim SH, Boyd SK, Koch LG, Britton SL, Hepple RT, Zernicke RF (2008) Differences in bone morphology in older female rats selectively bred for high and low aerobic capacity. In: Transactions of the 54th Annual Meeting of the Orthopaedic Research Society, San Francisco, CA, 33:0910
19.
go back to reference Myers J, Prakash M, Froelicher V, Do D, Partington S, Atwood JE (2002) Exercise capacity and mortality among men referred for exercise testing. N Engl J Med 346:793–801PubMedCrossRef Myers J, Prakash M, Froelicher V, Do D, Partington S, Atwood JE (2002) Exercise capacity and mortality among men referred for exercise testing. N Engl J Med 346:793–801PubMedCrossRef
20.
21.
go back to reference Wronski TJ, Cintron M, Dann LM (1988) Temporal relationship between bone loss and increased bone turnover in ovariectomized rats. Calcif Tissue Int 43:179–183PubMedCrossRef Wronski TJ, Cintron M, Dann LM (1988) Temporal relationship between bone loss and increased bone turnover in ovariectomized rats. Calcif Tissue Int 43:179–183PubMedCrossRef
22.
go back to reference Wronski TJ, Dann LM, Scott KS, Cintron M (1989) Long-term effects of ovariectomy and aging on the rat skeleton. Calcif Tissue Int 45:360–366PubMedCrossRef Wronski TJ, Dann LM, Scott KS, Cintron M (1989) Long-term effects of ovariectomy and aging on the rat skeleton. Calcif Tissue Int 45:360–366PubMedCrossRef
23.
go back to reference Lelovas PP, Xanthos TT, Thoma SE, Lyritis GP, Dontas IA (2008) The laboratory rat as an animal model for osteoporosis research. Comp Med 58:424–430PubMed Lelovas PP, Xanthos TT, Thoma SE, Lyritis GP, Dontas IA (2008) The laboratory rat as an animal model for osteoporosis research. Comp Med 58:424–430PubMed
24.
go back to reference Danielsen CC, Mosekilde L, Svenstrup B (1993) Cortical bone mass, composition, and mechanical properties in female rats in relation to age, long-term ovariectomy, and estrogen substitution. Calcif Tissue Int 52:26–33PubMedCrossRef Danielsen CC, Mosekilde L, Svenstrup B (1993) Cortical bone mass, composition, and mechanical properties in female rats in relation to age, long-term ovariectomy, and estrogen substitution. Calcif Tissue Int 52:26–33PubMedCrossRef
25.
go back to reference Mosekilde L, Sogaard CH, Danielsen CC, Torring O (1991) The anabolic effects of human parathyroid hormone (hPTH) on rat vertebral body mass are also reflected in the quality of bone, assessed by biomechanical testing: a comparison study between hPTH-(1–34) and hPTH-(1–84). Endocrinology 129:421–428PubMedCrossRef Mosekilde L, Sogaard CH, Danielsen CC, Torring O (1991) The anabolic effects of human parathyroid hormone (hPTH) on rat vertebral body mass are also reflected in the quality of bone, assessed by biomechanical testing: a comparison study between hPTH-(1–34) and hPTH-(1–84). Endocrinology 129:421–428PubMedCrossRef
26.
go back to reference Aerssens J, van Audekercke R, Talalaj M, Geusens P, Bramm E, Dequeker J (1996) Effect of 1alpha-vitamin D3 and estrogen therapy on cortical bone mechanical properties in the ovariectomized rat model. Endocrinology 137:1358–1364PubMedCrossRef Aerssens J, van Audekercke R, Talalaj M, Geusens P, Bramm E, Dequeker J (1996) Effect of 1alpha-vitamin D3 and estrogen therapy on cortical bone mechanical properties in the ovariectomized rat model. Endocrinology 137:1358–1364PubMedCrossRef
27.
go back to reference Hou JC, Zernicke RF, Barnard RJ (1991) Experimental diabetes, insulin treatment, and femoral neck morphology and biomechanics in rats. Clin Orthop Relat Res 264:278–285PubMed Hou JC, Zernicke RF, Barnard RJ (1991) Experimental diabetes, insulin treatment, and femoral neck morphology and biomechanics in rats. Clin Orthop Relat Res 264:278–285PubMed
28.
go back to reference Nakamura Y, Naito M, Hayashi K, Fotovati A, Abu-Ali S (2008) Effect of combined treatment with alendronate and calcitriol on femoral neck strength in osteopenic rats. J Orthop Surg Res 3:51PubMedCrossRef Nakamura Y, Naito M, Hayashi K, Fotovati A, Abu-Ali S (2008) Effect of combined treatment with alendronate and calcitriol on femoral neck strength in osteopenic rats. J Orthop Surg Res 3:51PubMedCrossRef
29.
go back to reference Sharkey NA, Lang DH, Okita N, Koch LG, Britton SL (2006) Differences in bone morphology in older female rats selectively bred for high and low aerobic capacity. In: Transactions of the 52nd Annual Meeting of the Orthopaedic Research Society. Chicago, IL, p 348 Sharkey NA, Lang DH, Okita N, Koch LG, Britton SL (2006) Differences in bone morphology in older female rats selectively bred for high and low aerobic capacity. In: Transactions of the 52nd Annual Meeting of the Orthopaedic Research Society. Chicago, IL, p 348
30.
go back to reference Oxlund BS, Ortoft G, Andreassen TT, Oxlund H (2003) Low-intensity, high-frequency vibration appears to prevent the decrease in strength of the femur and tibia associated with ovariectomy of adult rats. Bone 32:69–77PubMedCrossRef Oxlund BS, Ortoft G, Andreassen TT, Oxlund H (2003) Low-intensity, high-frequency vibration appears to prevent the decrease in strength of the femur and tibia associated with ovariectomy of adult rats. Bone 32:69–77PubMedCrossRef
31.
go back to reference Yao W, Hadi T, Jiang Y, Lotz J, Wronski TJ, Lane NE (2005) Basic fibroblast growth factor improves trabecular bone connectivity and bone strength in the lumbar vertebral body of osteopenic rats. Osteoporos Int 16:1939–1947PubMedCrossRef Yao W, Hadi T, Jiang Y, Lotz J, Wronski TJ, Lane NE (2005) Basic fibroblast growth factor improves trabecular bone connectivity and bone strength in the lumbar vertebral body of osteopenic rats. Osteoporos Int 16:1939–1947PubMedCrossRef
32.
go back to reference Andresen CJ, Moalli M, Turner CH, Berryman E, Pero R, Bagi CM (2008) Bone parameters are improved with intermittent dosing of vitamin D3 and calcitonin. Calcif Tissue Int 83:393–403PubMedCrossRef Andresen CJ, Moalli M, Turner CH, Berryman E, Pero R, Bagi CM (2008) Bone parameters are improved with intermittent dosing of vitamin D3 and calcitonin. Calcif Tissue Int 83:393–403PubMedCrossRef
33.
go back to reference Halonen NR, Tayim R, Goulet GC, Cole JH, Clifford C, Goldstein SA, Koch LG, Britton SL, Zernicke RF, Alford AI, Kozloff K (2010) Intrinsic aerobic capacity influences MSC proliferation, mineralization, and fracture healing. In: Transactions of the 56th Annual Meeting of the Orthopaedic Research Society, New Orleans, LA, 35:1712 Halonen NR, Tayim R, Goulet GC, Cole JH, Clifford C, Goldstein SA, Koch LG, Britton SL, Zernicke RF, Alford AI, Kozloff K (2010) Intrinsic aerobic capacity influences MSC proliferation, mineralization, and fracture healing. In: Transactions of the 56th Annual Meeting of the Orthopaedic Research Society, New Orleans, LA, 35:1712
34.
go back to reference Frost HM (1997) Obesity, and bone strength and “mass”: a tutorial based on insights from a new paradigm. Bone 21:211–214PubMedCrossRef Frost HM (1997) Obesity, and bone strength and “mass”: a tutorial based on insights from a new paradigm. Bone 21:211–214PubMedCrossRef
35.
go back to reference Novak CM, Escande C, Gerber SM, Chini EN, Zhang M, Britton SL, Koch LG, Levine JA (2009) Endurance capacity, not body size, determines physical activity levels: role of skeletal muscle PEPCK. PLoS One 4:e5869PubMedCrossRef Novak CM, Escande C, Gerber SM, Chini EN, Zhang M, Britton SL, Koch LG, Levine JA (2009) Endurance capacity, not body size, determines physical activity levels: role of skeletal muscle PEPCK. PLoS One 4:e5869PubMedCrossRef
36.
go back to reference Tou JC, Foley A, Yuan YV, Arnaud S, Wade CE, Brown M (2008) The effect of OVX combined with hindlimb unloading and reloading on the long bones of mature Sprague-Dawley rats. Menopause 15:494–502PubMedCrossRef Tou JC, Foley A, Yuan YV, Arnaud S, Wade CE, Brown M (2008) The effect of OVX combined with hindlimb unloading and reloading on the long bones of mature Sprague-Dawley rats. Menopause 15:494–502PubMedCrossRef
Metadata
Title
Osteoblast Response to Ovariectomy Is Enhanced in Intrinsically High Aerobic-Capacity Rats
Authors
G. C. Goulet
N. R. Halonen
L. G. Koch
S. L. Britton
R. F. Zernicke
K. M. Kozloff
Publication date
01-04-2011
Publisher
Springer-Verlag
Published in
Calcified Tissue International / Issue 4/2011
Print ISSN: 0171-967X
Electronic ISSN: 1432-0827
DOI
https://doi.org/10.1007/s00223-010-9457-x

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