Endogenous PKIγ limits the duration of the anti-apoptotic effects of pth and β-adrenergic agonists in osteoblasts

Journal of Bone and Mineral Research

Volumn 22, Issue 5, 2007, Pages 656-664

  Chen, Xin ^a   Song, In Hwan ^a,b   Dennis, James E ^a   Greenfield, Edward M ^a,c  

^a CASE WESTERN RESERVE UNIVERSITY   (United States)

^b Yeungnam University College of Medicine   (South Korea)

^c CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Apoptosis; Osteoblast; Protein kinase inhibitor ; PTH; adrenergic agonists

Indexed keywords

BETA ADRENERGIC RECEPTOR; COMPLEMENTARY DNA; CYCLIC AMP; CYCLIC AMP DEPENDENT PROTEIN KINASE; ISOPRENALINE; PARATHYROID HORMONE; PROTEIN KINASE INHIBITOR; PROTEIN KINASE INHIBITOR GAMMA; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; BETA ADRENERGIC RECEPTOR STIMULATING AGENT; PKIGAMMA PROTEIN, RAT; SIGNAL PEPTIDE;

ANIMAL CELL; APOPTOSIS; ARTICLE; CELL CULTURE; CELL LINE; CONTROLLED STUDY; CULTURE MEDIUM; GENE EXPRESSION REGULATION; NONHUMAN; OSTEOBLAST; OSTEOPOROSIS; PROTEIN FUNCTION; RAT; SIGNAL TRANSDUCTION; ANIMAL; DRUG EFFECT; GENETICS; METABOLISM; TUMOR CELL LINE;

ADRENERGIC BETA-AGONISTS; ANIMALS; APOPTOSIS; CELL LINE, TUMOR; CYCLIC AMP-DEPENDENT PROTEIN KINASES; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; OSTEOBLASTS; OSTEOPOROSIS; PARATHYROID HORMONE; RATS; RNA, SMALL INTERFERING; SIGNAL TRANSDUCTION;

EID: 34447550713     PISSN: 08840431     EISSN: None     Source Type: Journal    
DOI: 10.1359/jbmr.070122     Document Type: Article

References (71)

1. 1 Tam CS, Heersche JNM, Murray TM, Parsons JA 1982 Parathyroid hormone stimulates the bone apposition rate independently of its resorptive action: Differential effects of intermittent and continuous administration. Endocrinology 110: 506–512.
2. 2 Dempster DW, Cosman F, Parisien M, Shen V, Lindsay R 1993 Anabolic actions of parathyroid hormone on bone. Endocrinol Rev 14: 690–709.
3. 3 Bellido T, Ali A, Plotkin L, Fu Q, Gubrij I, Roberson P, Weinstein R, O'Brien C, Manolagas S, Jilka R 2003 Proteasomal degradation of Runx2 shortens parathyroid hormone‐induced anti‐apoptotic signaling in osteoblasts. A putative explanation for why intermittent administration is needed for bone anabolism. J Biol Chem 278: 50259–50272.
4. 4 Schmidt IU, Dobnig H, Turner RT 1995 Intermittent parathyroid hormone treatment increases osteoblast number, steady state messenger ribonucleic acid levels for osteocalcin, and bone formation in tibial metaphysis of hypophysectomized female rats. Endocrinology 136: 5127–5134.
5. 5 Hodsman AB, Fraher LJ, Ostbye T, Adachi JD, Steer BM 1993 An evaluation of several biochemical markers for bone formation and resorption in a protocol utilizing cyclical parathyroid hormone and calcitonin therapy for osteoporosis. J Clin Invest 91: 1138–1148.
6. 6 Nishida S, Yamaguchi A, Tanizawa T, Endo N, Mashiba T, Uchiyama Y, Suda T, Yoshiki S, Takahashi HE 1994 Increased bone formation by intermittent parathyroid hormone administration is due to stimulation of proliferation and differentiation of osteoprogenitor cells in bone marrow. Bone 15: 717–723.
7. 7 Kostenuik PJ, Halloran BP, Turner RT, Morey‐Holton ER, Bikle DD 1999 Skeletal unloading causes resistance of osteoprogenitor cells to parathyroid hormone and to insulin‐like growth factor‐I. J Bone Miner Res 14: 21–31.
8. 8 Dobnig H, Turner RT 1995 Evidence that intermittent treatment with parathyroid hormone increases bone formation in adult rates by activation of bone lining cells. Endocrinology 136: 3632–3638.
9. 9 Dobnig H, Turner RT 1997 The effects of programmed administration of human parathyroid hormone fragment (1‐34) on bone histomorphometry and serum chemistry in rats. Endocrinology 138: 4607–4612.
10. 10 Jilka RL, Weinstein RS, Bellido T, Parfitt AM, Manolagas SC 1998 Osteoblast programmed cell death (apoptosis): Modulation by growth factors and cytokines. J Bone Miner Res 13: 793–802.
11. 11 Jilka RL, Weinstein RS, Bellido T, Roberson P, Parfitt AM, Manolagas S 1999 Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone. J Clin Invest 104: 439–446.
12. 12 Chen HL, Demiralp B, Schneider A, Koh AJ, Wang CCS, Mc CY, Cauley LK 2002 Parathyroid hormone and parathyroid hormone‐related protein exert both pro‐ and anti‐apoptotic effects in mesenchymal cells. J Biol Chem 277: 19374–19381.
13. 13 Sowa H, Kaji H, Iu MF, Tsukamoto T, Sugimoto T, Chihara K 2003 Parathyroid hormone‐Smad3 axis exerts anti‐apoptotic action and augments anabolic action of transforming growth factor beta in osteoblasts. J Biol Chem 278: 52240–52252.
14. 14 Babij P, Zhao W, Small C, Kharode Y, Yaworsky PJ, Bouxsein ML, Reddy PS, Bodine PV, Robinson JA, Bhat B, Marzolf J, Moran RA, Bex F 2003 High bone mass in mice expressing a mutant LRP5 gene. J Bone Miner Res 18: 960–974.
15. 15 Kousteni S, Chen JR, Bellido T, Han L, Ali AA, O'Brien CA, Plotkin L, Fu Q, Mancino AT, Wen Y, Vertino AM, Powers CC, Stewart SA, Ebert R, Parfitt AM, Weinstein RS, Jilka RL, Manolagas SC 2002 Reversal of bone loss in mice by nongenotropic signaling of sex steroids. Science 298: 843–846.
16. 16 Centrella M, McCarthy TL, Chang WZ, Labaree DC, Hochberg RB 2004 Estren (4‐estren‐3alpha,17beta‐diol) is a prohormone that regulates both androgenic and estrogenic transcriptional effects through the androgen receptor. Mol Endocrinol 18: 1120–1130.
17. 17 Greenfield EM, Shaw SM, Gornik SA, Banks MA 1995 Adenyl cyclase and interleukin 6 are downstream effectors of parathyroid hormone resulting in stimulation of bone resorption. J Clin Invest 96: 1238–1244.
18. 18 Partridge NC, Bloch SR, Pearman AT 1994 Signal transduction pathways mediating parathyroid hormone regulation of osteoblastic gene expression. J Cell Biochem 55: 321–327.
19. 19 Rixon RH, Whitfield JF, Gagnon L, Isaacs RJ, Maclean S, Chakravarthy B, Durkin JP, Neugebauer W, Ross V, Sung W, Willick GE 1994 Parathyroid hormone fragments may stimulate bone growth in ovariectomized rats by activating adenylyl cyclase. J Bone Miner Res 9: 1179–1189.
20. 20 Armamento‐Villareal R, Ziambaras K, Abbasi‐Jarhomi SH, Dimarogonas A, Halstead L, Fausto A, Avioli LV, Civitelli R 1997 An intact N terminus is required for the anabolic action of parathyroid hormone on adult female rats. J Bone Miner Res 12: 384–392.
21. 21 Qin L, Raggatt LJ, Partridge NC 2004 Parathyroid hormone: A double‐edged sword for bone metabolism. Trends Endocrinol Metab 15: 60–65.
22. 22 Swarthout JT, D'Alonzo RC, Selvamurugan N, Partridge NC 2002 Parathyroid hormone‐dependent signaling pathways regulating genes in bone cells. Gene 282: 1–17.
23. 23 Walsh DA, Patten SMV 1994 Multiple pathway signal transduction by the cAMP‐dependent protein kinase. FASEB J 8: 1227–1236.
24. 24 Greenfield EM, Horowitz MC, Lavish SA 1996 Stimulation by parathyroid hormone of interleukin‐6 and leukemia inhibitory factor expression in osteoblasts is an immediate‐early gene response induced by cAMP signal transduction. J Biol Chem 271: 10984–10989.
25. 25 Chen X, Dai JC, Greenfield EM 2002 Termination of immediate‐early gene expression after stimulation by parathyroid hormone or isoproterenol. Am J Physiol Cell Physiol 283: C1432–C1440.
26. 26 Chen X, Dai JC, Orellana SA, Greenfield EM 2005 Endogenous protein kinase inhibitorγ terminates immediate‐early gene expression induced by cAMP‐dependent protein kinase (PKA) signaling: Termination depends on PKA inactivation rather than PKA export from the nucleus. J Biol Chem 280: 2700–2707.
27. 27 Demiralp B, Chen HL, Koh AJ, Keller ET, McCauley LK 2002 Anabolic actions of parathyroid hormone during bone growth are dependent on c‐fos. Endocrinology 143: 4038–4047.
28. 28 Walsh DA, Angelos KL, Patten SMV, Glass DB, Garetto LP 1990 The inhibitor protein of the cAMP‐dependent protein kinase. Kemp BE (ed.) Peptides and Protein Phosphorylation. CRC Press, Boca Raton, FL, USA, 43–84.
29. 29 Dalton GD, Dewey WL 2006 Protein kinase inhibitor peptide (PKI): A family of endogenous neuropeptides that modulate neuronal cAMP‐dependent protein kinase function. Neuropeptides 40: 23–34.
30. 30 Collins SP, Uhler MD 1997 Characterization of PKIγ, a novel isoform of the protein kinase inhibitor of cAMP‐dependent protein kinase. J Biol Chem 272: 18169–18178.
31. 31 Zhao L, Yang S, Zhou G, Yang J, Ji D, Sabatakos G, Zhu T 2006 Downregulation of cAMP‐dependent protein kinase inhibitor gamma is required for BMP‐2‐induced osteoblastic differentiation. Int J Biochem Cell Biol 38: 2064–2073.
32. 32 Gangolli EA, Belyamani M, Muchinsky S, Narula A, Burton KA, McKnight GS, Uhler MD, Idzerda RL 2000 Deficient gene expression in protein kinase inhibitor alpha Null mutant mice. Mol Cell Biol 20: 3442–3448.
33. 33 Belyamani M, Gangolli EA, Idzerda RL 2001 Reproductive function in protein kinase inhibitor‐deficient mice. Mol Cell Biol 21: 3959–3963.
34. 34 Nalepka JL, Greenfield EM 2004 Detection of bacterial endotoxin in human tissues. Biotechniques 37: 413–417.
35. 35 Majeska RJ, Rodan SB, Rodan GA 1980 Parathyroid hormone‐responsive clonal cell lines from rat osteosarcoma. Endocrinology 107: 1494–1503.
36. 36 Dai JC, He P, Chen X, Greenfield EM 2006 TNFα and PTH utilize distinct mechanisms to induce IL‐6 and RANKL expression with markedly different kinetics. Bone 38: 509–520.
37. 37 Yamamoto T, Kambe F, Cao X, Lu X, Ishiguro N, Seo H 2007 Parathyroid hormone activates phosphoinositide 3‐kinase‐Akt‐Bad cascade in osteoblast‐like cells. Bone 40: 354–359.
38. 38 Pollock JH, Blaha MJ, Gornik SA, Stevenson S, Greenfield EM 1996 In vivo demonstration that parathyroid hormone and parathyroid hormone‐related protein stimulate expression by osteoblasts of interleukin‐6 and leukemia inhibitory factor. J Bone Miner Res 11: 754–759.
39. 39 Kellenberger S, Muller K, Richener H, Bilbe G 1998 Formoterol and isoproterenol induce c‐fos gene expression in osteoblast‐like cells by activating beta2‐adrenergic receptors. Bone 22: 471–478.
40. 40 Onishi Y, Azuma Y, Sato Y, Mizuno Y, Tadakuma T, Kizaki H 1993 Topoisomerase inhibitors induce apoptosis in thymocytes. Biochim Biophys Acta 1175: 147–154.
41. 41 Reynolds RM, Dennison EM, Walker BR, Syddall HE, Wood PJ, Andrew R, Phillips DI, Cooper C 2005 Cortisol secretion and rate of bone loss in a population‐based cohort of elderly men and women. Calcif Tissue Int 77: 134–138.
42. 42 Buxton EC, Yao W, Lane NE 2004 Changes in serum receptor activator of nuclear factor‐kappaB ligand, osteoprotegerin, and interleukin‐6 levels in patients with glucocorticoid‐induced osteoporosis treated with human parathyroid hormone (1–34). J Clin Endocrinol Metab 89: 3332–3336.
43. 43 Rosen CJ 2005 The role of parathyroid hormone in the management of osteoporosis. Horm Res 64 (Suppl 2): 81–85.
44. 44 Sellmeyer D, Palermo L, Bouzsein M, Bilezikian J, Greenspan S, Ensrud K, Black D, Rosen C 2004 Heterogeneity in skeletal response to full‐length parathyroid hormone (PTH). J Bone Miner Res 19: S96.
45. 45 Lane N, Sanchez S, Genant H, Jenkins D, Arnaud C 2000 Short‐term increases in bone turnover markers predict parathyroid hormone‐induced spinal bone mineral density gains in postmenopausal women with glucocorticoid‐induced osteoporosis. Osteoporos Int 11: 434–442.
46. 46 Chen P, Satterwhite J, Licata A, Lewiecki E, Sipos A, Misurski D, Wagman R 2005 Early changes in biochemical markers of bone formation predict BMD response to teriparatide in postmenopausal women with osteoporosis. J Bone Miner Res 20: 962–970.
47. 47 Lee SK, Lorenzo JA 1999 Parathyroid hormone stimulates TRANCE and inhibits osteoprotegerin messenger ribonucleic acid expression in murine bone marrow cultures: Correlation with osteoclast‐like cell formation. Endocrinology 140: 3552–3561.
48. 48 Ma YL, Cain RL, Halladay DL, Yang X, Zeng Q, Miles RR, Chandrasekhar S, Martin TJ, Onyia JE 2001 Catabolic effects of continuous human PTH (1–38) in vivo is associated with sustained stimulation of RANKL and inhibition of osteoprotegerin and gene‐associated bone formation. Endocrinology 142: 4047–4054.
49. 49 Horwood NJ, Elliott J, Martin TJ, Gillespie MT 1998 Osteotropic agents regulate the expression of osteoclast differentiation factor and osteoprotegerin in osteoblastic stromal cells. Endocrinology 139: 4743–4746.
50. 50 Takeda S, Elefteriou F, Levasseur R, Liu X, Zhao L, Parker K, Armstrong D, Ducy P, Karsenty G 2002 Leptin regulates bone formation via the sympathetic nervous system. Cell 111: 305–317.
51. 51 Pierroz DD, Bouxsein ML, Rizzoli R, Ferrari SL 2006 Combined treatment with a beta‐blocker and intermittent PTH improves bone mass and microarchitecture in ovariectomized mice. Bone 39: 260–267.
52. 52 Minkowitz B, Boskey AL, Lane JM, Pearlman HS, Vigorita VJ 1991 Effects of propranolol on bone metabolism in the rat. J Orthop Res 9: 869–875.
53. 53 Pasco JA, Henry MJ, Nicholson GC, Schneider HG, Kotowicz MA 2005 Beta‐blockers reduce bone resorption marker in early postmenopausal women. Ann Hum Biol 32: 738–745.
54. 54 Pasco JA, Henry MJ, Sanders KM, Kotowicz MA, Seeman E, Nicholson GC 2004 Beta‐adrenergic blockers reduce the risk of fracture partly by increasing bone mineral density: Geelong Osteoporosis Study. J Bone Miner Res 19: 19–24.
55. 55 Bonnet N, Gadois C, Lemineur G, Lespessailles E, Courteix D, Benhamou L 2005 Beta blockers reduce the prevalence of fracture: Influence on bone mineral density, bone geometry and microarchitecture. J Bone Miner Res 20: S89.
56. 56 Schlienger RG, Kraenzlin ME, Jick SS, Meier CR 2004 Use of beta‐blockers and risk of fractures. JAMA 292: 1326–1332.
57. 57 Turker S, Karatosun V, Gunal I 2006 Beta‐blockers increase bone mineral density. Clin Orthop 443: 73–74.
58. 58 Rejnmark L, Vestergaard P, Kassem M, Christoffersen BR, Kolthoff N, Brixen K, Mosekilde L 2004 Fracture risk in perimenopausal women treated with beta‐blockers. Calcif Tissue Int 75: 365–372.
59. 59 Levasseur R, Dargent‐Molina P, Sabatier JP, Marcelli C, Breart G 2005 Beta‐blocker use, bone mineral density, and fracture risk in older women: Results from the Epidemiologie de l'Osteoporose prospective study. J Am Geriatr Soc 53: 550–552.
60. 60 Reid IR, Gamble GD, Grey AB, Black DM, Ensrud KE, Browner WS, Bauer DC 2005 beta‐Blocker use, BMD, and fractures in the study of osteoporotic fractures. J Bone Miner Res 20: 613–618.
61. 61 Reid IR, Lucas J, Wattie D, Horne A, Bolland M, Gamble GD, Davidson JS, Grey AB 2005 Effects of a beta‐blocker on bone turnover in normal postmenopausal women: A randomized controlled trial. J Clin Endocrinol Metab 90: 5212–5216.
62. 62 Pierroz DD, Muzzin P, Bouxsein ML, Rizzoli R, Ferrari SL 2005 Mice null for beta 1 beta 2‐adrenergic receptors have low bone mass and architecture and are resistant to isoproterenol‐induced inhibition of bone growth. Bone 36: S130–S131.
63. 63 Pataki A, Muller K, Bilbe G, Green JR, Glatt M 1996 Anabolic effects of beta2‐agonists, formoterol and salbutamol on cancellous bone of ovariectomized (OVX) rat. Bone 19: S158.
64. 64 Martin MC, Dransfield I, Haslett C, Rossi AG 2001 Cyclic AMP regulation of neutrophil apoptosis occurs via a novel protein kinase A‐independent signaling pathway. J Biol Chem 276: 45041–45045.
65. 65 Tse R, Marroquin BA, Dorscheid DR, White SR 2003 Beta‐adrenergic agonists inhibit corticosteroid‐induced apoptosis of airway epithelial cells. Am J Physiol Lung Cell Mol Physiol 285: L393–L404.
66. 66 Machida K, Inoue H, Matsumoto K, Tsuda M, Fukuyama S, Koto H, Aizawa H, Kureishi Y, Hara N, Nakanishi Y 2005 Activation of PI3K‐Akt pathway mediates antiapoptotic effects of beta‐adrenergic agonist in airway eosinophils. Am J Physiol Lung Cell Mol Physiol 288: L860–L867.
67. 67 Yamashita J, Chun YP, Datta NS, McCauley LK 2005 The evidence that Bcl‐2 is dispensable for the anabolic action of PTH in bone. J Bone Miner Res 20: S76.
68. 68 Gregorio GD, Coppa A, Cosentino C, Ucci S, Messina S, Nicolussi A, D'Inzeo S, Pardo AD, Avvedimento EV, Porcellini A 2006 The p85 regulatory subunit of PI3K mediates TSH‐cAMP‐PKA growth and survival signals. Oncogene (in press).
69. 69 Cosentino C, Domenico MD, Porcellini A, Cuozzo C, Gregorio GD, Santillo MR, Agnese S, Stasio RD, Feliciello A, Migliaccio A, Avvedimento EV 2006 p85 regulatory subunit of PI3K mediates cAMP‐PKA and estrogens biological effects on growth and survival. Oncogene (in press).
70. 70 Tintut Y, Parhami F, Le V, Karsenty G, Demer LL 1999 Inhibition of osteoblast‐specific transcription factor Cbfa1 by the cAMP pathway in osteoblastic cells. Ubiquitin/proteasome‐dependent regulation. J Biol Chem 274: 28875–28879.
71. 71 Martin MC, Allan LA, Lickrish M, Sampson C, Morrice N, Clarke PR 2005 Protein kinase A regulates caspase‐9 activation by Apaf‐1 downstream of cytochrome c. J Biol Chem 280: 15449–15455.