54. Dufour, C., X. Holy, and P.J. Marie, Skeletal unloading induces osteoblastapoptosis and targets alpha5beta1-PI3K-Bcl-2 signaling in rat bone. Exp CellRes, 2007. 313(2): p. 394-403.55. Jilka, R.L., et al., Increased bone formation by prevention of osteoblast apoptosiswith parathyroid hormone. J Clin Invest, 1999. 104(4): p. 439-46.56. Turner, R.T., et al., Dose-response effects of intermittent PTH on cancellousbone in hindlimb unloaded rats. J Bone Miner Res, 2007. 22(1): p. 64-71.57. Kousteni, S., et al., Reversal of bone loss in mice by nongenotropic signaling ofsex steroids. Science, 2002. 298(5594): p. 843-6.58. Oktem, G., et al., Evaluation of the relationship between inducible nitric oxidesynthase (iNOS) activity and effects of melatonin in experimental osteoporosis inthe rat. Surg Radiol Anat, 2006. 28(2): p. 157-62.59. Bikle, D.D., T. Sakata, and B.P. Halloran, The impact of skeletal unloading onbone formation. Gravit Space Biol Bull, 2003. 16(2): p. 45-54.60. Rucci, N., et al., Modeled microgravity stimulates osteoclastogenesis and boneresorption by increasing osteoblast RANKL/OPG ratio. J Cell Biochem, 2007.100(2): p. 464-73.61. Nakamura, H., et al., Suppression of osteoblastic phenotypes and modulation ofpro- and anti-apoptotic features in normal human osteoblastic cells under avector-averaged gravity condition. J Med Dent Sci, 2003. 50(2): p. 167-76.62. Bucaro, M.A., et al., The effect of simulated microgravity on osteoblasts isindependent of the induction of apoptosis. J Cell Biochem, 2007. 102(2): p. 483-95.63. Reiman, M.P., M.E. Rogers, and R.C. Manske, Interlimb differences in lowerextremity bone mineral density following anterior cruciate ligamentreconstruction. J Orthop Sports Phys Ther, 2006. 36(11): p. 837-44.64. Smith, S.M., et al., WISE-2005: supine treadmill exercise within lower bodynegative pressure and flywheel resistive exercise as a countermeasure to bedrest-induced bone loss in women during 60-day simulated microgravity. Bone,2008. 42(3): p. 572-81.65. Spector, E.R., S.M. Smith, and J.D. Sibonga, Skeletal effects of long-durationhead-down bed rest. Aviat Space Environ Med, 2009. 80(5 Suppl): p. A23-8.66. Yazicioglu, K., et al., Osteoporosis: A factor on residual limb pain in traumatictrans-tibial amputations. Prosthet Orthot Int, 2008. 32(2): p. 172-8.67. Luria, T., et al., Effects of a prolonged submersion on bone strength andmetabolism in young healthy submariners. Calcif Tissue Int, 2010. 86(1): p. 8-13.140
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EXPLORATION OF THE ROLE OF SERUM FA
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Table of contentsIndex of Figures .
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Chapter Four - Attempts to find an
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Index of figures1.1. Simplified sch
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6.17. Longitudinal analysis of OPG
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6.49. Longitudinal analysis of ColI
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A.2. Complete list of BSALP correla
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List of abbreviationsα-MEM. Alpha-
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PCR. Polymerase chain reactionPer1
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G2/M checkpoint. The point in the c
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Species names13-lined ground squirr
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Chapter One - Background and signif
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1.3 Bone turnover is unbalanced dur
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pro-apoptosis regulator BAX. An imp
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low-dose administration of parathyr
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decrease in bone trabecular thickne
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experience periodic arousals in whi
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ears must have evolved a mechanism
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1.7.6 Hypothesis 2: OCN interacts w
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ain, heart, and femoral muscle of h
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Hypothesis 3a: Serum concentrations
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were released. Behavior indicating
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2.3 ResultsSerum activity of the bo
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(p
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post-hibernation sampling in the be
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also unclear whether ucOCN may affe
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atios of intact to fragmented OCN m
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Table 2.3—Bone marker “seasonal
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Table 2.7—Chemistry panel “seas
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ABNormalized BSALPBSALP (U/L)CO N D
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Total Calcium (mg/dL)A1.21.151.11.0
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ABTotal OCN (ng/mL)150100500O N D J
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Adiponectin (ng/mL)AB40003500300025
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ABNormalized InsulinInsulin (μU/mL
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surrounding and encompassing hibern
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decreased from 788+30 ng/mL in preh
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120-122]. Most small hibernators ar
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ears. Similarly, serum NPY increase
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Table 3.2—Serum factor longitudin
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Leptin (ng/mL)ABO N D J F M A M O N
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Norepinephrine (ng/mL)A807060504030
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IGF‐1 (ng/mL)AN D J F M A MB10009
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2008. Samples were collected as des
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sampling points. It is possible to
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C‐Terminal PTH (Relative)AB504030
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Chapter Five — Serum from hiberna
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Synergy HT Multi-Detection Micropla
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gene specific primers and 12.5 μL
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involved in the reduced caspase-3/7
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hibernation cycles without problem
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filtered seasonal bear serum and fo
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which is dependent upon caspase-3 a
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Caspase‐3/7 ActivityO N D J F M A
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6Caspase‐3/7 Activity54321**0Vehi
- Page 111 and 112: ABCaspase‐3/7 Activity9876543210*
- Page 113 and 114: eyond the G1/S checkpoint, thus ind
- Page 115 and 116: ears, it is possible that tissue se
- Page 117 and 118: PTH1R, RANKL, Runx2, Smurf1, TLR4,
- Page 119 and 120: factors Runx2 and OCN also increase
- Page 121 and 122: Table 6.3—Gene expression 3 hour
- Page 123 and 124: Table 6.5—Gene expression 6 day d
- Page 125 and 126: Cyclin D1 Gene ExpressionO N D J F
- Page 127 and 128: Smurf1 Gene ExpressionO N D J F M A
- Page 129 and 130: BAK Gene ExpressionO N D J F M A MM
- Page 131 and 132: M‐CSF Gene ExpressionO N D J F M
- Page 133 and 134: Per1 Gene ExpressionO N D J F M A M
- Page 135 and 136: Akt Gene ExpressionO N D J F M A MM
- Page 137 and 138: Bcl‐2 Gene ExpressionO N D J F M
- Page 139 and 140: Cyclin D1 Gene ExpressionO N D J F
- Page 141 and 142: OPN Gene ExpressionO N D J F M A MM
- Page 143 and 144: 2PTH1R Gene Expression1.510.50O N D
- Page 145 and 146: TLR4 Gene ExpressionO N D J F M A M
- Page 147 and 148: Bcl‐2 Gene ExpressionO N D J F M
- Page 149 and 150: OCN Gene ExpressionO N D J F M A MM
- Page 151 and 152: PTH1R Gene ExpressionO N D J F M A
- Page 153 and 154: TLR4 Gene ExpressionO N D J F M A M
- Page 155 and 156: condition in renal patients in whic
- Page 157 and 158: hibernation. This report brings to
- Page 159 and 160: 14. Kaneps, A.J., S.M. Stover, and
- Page 161: 41. Chowdhury, I., B. Tharakan, and
- Page 165 and 166: 95. Perrien, D.S., et al., Aging al
- Page 167 and 168: 122. Lesser, R.W., et al., Renal re
- Page 169 and 170: 151. Confavreux, C.B., R.L. Levine,
- Page 171 and 172: 178. Toribara, T.Y., A.R. Terepka,
- Page 173 and 174: 206. Luo, X.H., et al., Adiponectin
- Page 175 and 176: 233. Florant, G.L., et al., Fat-cel
- Page 177 and 178: 259. Bhasin, S., et al., Older men
- Page 179 and 180: 284. Miura, M., et al., A crucial r
- Page 181 and 182: Appendix A—Complete tables of cor
- Page 183 and 184: Table A.5—Complete list of ionize
- Page 185 and 186: Table A.7—Complete list of adipon
- Page 187 and 188: Table A.12—Complete list of norep