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Current Osteoporosis Reports
Erschienen in: Current Osteoporosis Reports 4/2014

01.12.2014 | Skeletal Development (E Schipani and E Zelzer, Section Editors)

Aerobic Glycolysis in Osteoblasts

verfasst von: Emel Esen, Fanxin Long

Erschienen in: Current Osteoporosis Reports | Ausgabe 4/2014

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Abstract

Osteoblasts, the chief bone-making cells in the body, are a focus of osteoporosis research. Although teriparatide, a synthetic fragment of the human parathyroid hormone (PTH), has been an effective bone anabolic drug, there remains a clinical need for additional therapeutics that safely stimulates osteoblast number and function. Work in the past several decades has provided unprecedented clarity about the roles of growth factors and transcription factors in regulating osteoblast differentiation and activity, but whether these factors may regulate cellular metabolism to influence cell fate and function has been largely unexplored. The past few years have witnessed a resurgence of interest in the cellular metabolism of osteoblasts, with the hope that elucidation of their metabolic profile may open new avenues for developing bone anabolic agents. Here we review the current understanding about glucose metabolism in osteoblasts.
Literatur
1.
Long F. Building strong bones: molecular regulation of the osteoblast lineage. Nat Rev Mol Cell Biol. 2012;13(1):27–38.CrossRef
2.
3.
Teitelbaum SL, Ross FP. Genetic regulation of osteoclast development and function. Nat Rev Genet. 2003;4(8):638–49.PubMedCrossRef
4.
Feng JQ, Clinkenbeard EL, Yuan B, White KE, Drezner MK. Osteocyte regulation of phosphate homeostasis and bone mineralization underlies the pathophysiology of the heritable disorders of rickets and osteomalacia. Bone. 2013;54(2):213–21.PubMedCrossRefPubMedCentral
5.
Clemens TL, Karsenty G. The osteoblast: an insulin target cell controlling glucose homeostasis. J Bone Miner Res. 2011;26(4):677–80.PubMedCrossRef
6.
Bell GI, Burant CF, Takeda J, Gould GW. Structure and function of mammalian facilitative sugar transporters. J Biol Chem. 1993;268(26):19161–4.PubMed
7.
8.
Bouche C, Serdy S, Kahn CR, Goldfine AB. The cellular fate of glucose and its relevance in type 2 diabetes. Endocr Rev. 2004;25(5):807–30.PubMedCrossRef
9.
Kopperschlager G, Kirchberger J. Methods for the separation of lactate dehydrogenases and clinical significance of the enzyme. J Chromatogr B Biomed Appl. 1996;684(1–2):25–49.PubMedCrossRef
10.
Perl A, Hanczko R, Telarico T, Oaks Z, Landas S. Oxidative stress, inflammation and carcinogenesis are controlled through the pentose phosphate pathway by transaldolase. Trends Mol Med. 2011;17(7):395–403.PubMedCrossRefPubMedCentral
11.
Wamelink MM, Struys EA, Jakobs C. The biochemistry, metabolism and inherited defects of the pentose phosphate pathway: a review. J Inherit Metab Dis. 2008;31(6):703–17.PubMedCrossRef
12.
Teo CF, Wollaston-Hayden EE, Wells L. Hexosamine flux, the O-GlcNAc modification, and the development of insulin resistance in adipocytes. Mol Cell Endocrinol. 2010;318(1–2):44–53.PubMedCrossRefPubMedCentral
13.
Thomas DM, Rogers SD, Ng KW, Best JD. Dexamethasone modulates insulin receptor expression and subcellular distribution of the glucose transporter GLUT 1 in UMR 106-01, a clonal osteogenic sarcoma cell line. J Mol Endocrinol. 1996;17(1):7–17.PubMedCrossRef
14.
Thomas DM, Maher F, Rogers SD, Best JD. Expression and regulation by insulin of GLUT 3 in UMR 106-01, a clonal rat osteosarcoma cell line. Biochem Biophys Res Commun. 1996;218(3):789–93.PubMedCrossRef
15.
Rolland F, Winderickx J, Thevelein JM. Glucose-sensing mechanisms in eukaryotic cells. Trends Biochem Sci. 2001;26(5):310–7.PubMedCrossRef
16.
Borle AB, Nichols N, Nichols Jr G. Metabolic studies of bone in vitro. I. Normal bone. J Biol Chem. 1960;235:1206–10.PubMed
17.
Cohn DV, Forscher BK. Aerobic metabolism of glucose by bone. J Biol Chem. 1962;237:615–8.PubMed
18.
Flanagan B, Nichols Jr G. Metabolic studies of bone in vitro. V. glucose metabolism and collagen biosynthesis. J Biol Chem. 1964;239:1261–5.PubMed
19.
Peck WA, Birge Jr SJ, Fedak SA. Bone cells: biochemical and biological studies after enzymatic isolation. Science. 1964;146(3650):1476–7.PubMedCrossRef
20.•
Guntur AR, Le PT, Farber CR, Rosen CJ. Bioenergetics during calvarial osteoblast differentiation reflect strain differences in bone mass. Endocrinology. 2014;155(5):1589–95. This study shows that both glycolysis and oxygen comsumption increase during calvarial osteoblast differentiation but mature osteoblasts are more dependent on glycolysis. In addition, oxygen consumption rates in calvarial osteoblast cultures positively correlate with bone formation rate in vivo across different inbred mouse strains.
21.•
Regan JN, Lim J, Shi Y, et al. Up-regulation of glycolytic metabolism is required for HIF1alpha-driven bone formation. Proc Natl Acad Sci U S A. 2014;111(23):8673–8. This work provides evidence that increased glycolysis contributes to more robust cancellous bone formation in the mouse.PubMedCrossRef
22.
23.
Gatenby RA, Gillies RJ. Why do cancers have high aerobic glycolysis? Nat Rev Cancer. 2004;4(11):891–9.PubMedCrossRef
24.
Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324(5930):1029–33.PubMedCrossRefPubMedCentral
25.
26.
Costello LC, Franklin RB, Reynolds MA, Chellaiah M. The important role of osteoblasts and citrate production in bone formation: “Osteoblast Citration” as a new concept for an old relationship. Open Bone J. 2012;4.
27.
Hu YY, Rawal A, Schmidt-Rohr K. Strongly bound citrate stabilizes the apatite nanocrystals in bone. Proc Natl Acad Sci U S A. 2010;107(52):22425–9.PubMedCrossRefPubMedCentral
28.
Kenny AD, Draskoczy PR, Goldhaber P. Citric acid production by resorbing bone in tissue culture. Am J Physiol. 1959;197:502–4.PubMed
29.
30.
Costello LC, Liu Y, Franklin RB, Kennedy MC. Zinc inhibition of mitochondrial aconitase and its importance in citrate metabolism of prostate epithelial cells. J Biol Chem. 1997;272(46):28875–81.PubMedCrossRef
31.
Alhava EM, Olkkonen H, Puittinen J, Nokso-Koivisto VM. Zinc content of human cancellous bone. Acta Orthop Scand. 1977;48(1):1–4.PubMedCrossRef
32.
Inoue K, Matsuda K, Itoh M, et al. Osteopenia and male-specific sudden cardiac death in mice lacking a zinc transporter gene, Znt5. Hum Mol Genet. 2002;11(15):1775–84.PubMedCrossRef
33.
Tang Z, Sahu SN, Khadeer MA, Bai G, Franklin RB, Gupta A. Overexpression of the ZIP1 zinc transporter induces an osteogenic phenotype in mesenchymal stem cells. Bone. 2006;38(2):181–98.PubMedCrossRef
34.
Borle AB, Nichols N, Nichols Jr G. Metabolic studies of bone in vitro. II. The metabolic patterns of accretion and resorption. J Biol Chem. 1960;235:1211–4.PubMed
35.
Neuman WF, Neuman MW, Brommage R. Aerobic glycolysis in bone: lactate production and gradients in calvaria. Am J Physiol. 1978;234(1):C41–50.PubMed
36.
Rodan GA, Rodan SB, Marks Jr SC. Parathyroid hormone stimulation of adenylate cyclase activity and lactic acid accumulation in calvaria of osteopetrotic (ia) rats. Endocrinology. 1978;102(5):1501–5.PubMedCrossRef
37.
Zoidis E, Ghirlanda-Keller C, Schmid C. Stimulation of glucose transport in osteoblastic cells by parathyroid hormone and insulin-like growth factor I. Mol Cell Biochem. 2011;348(1–2):33–42.PubMedCrossRef
38.
Maupin KA, Droscha CJ, Williams BO. A comprehensive overview of skeletal phenotypes associated with alterations in Wnt/b-catenin signaling in humans and mice. Bone Res. 2013;1(1):27–71.CrossRef
39.•
Esen E, Chen J, Karner CM, Okunade AL, Patterson BW, Long F. WNT-LRP5 signaling induces Warburg effect through mTORC2 activation during osteoblast differentiation. Cell Metab. 2013;17(5):745–55. This work provides evidence that Wnt signaling directly stimulates aerobic glycolysis during osteoblast differentiation.PubMedCrossRefPubMedCentral
40.
Kemink SA, Hermus AR, Swinkels LM, Lutterman JA, Smals AG. Osteopenia in insulin-dependent diabetes mellitus; prevalence and aspects of pathophysiology. J Endocrinol Investig. 2000;23(5):295–303.CrossRef
41.
Nicodemus KK, Folsom AR. Type 1 and type 2 diabetes and incident hip fractures in postmenopausal women. Diabetes Care. 2001;24(7):1192–7.PubMedCrossRef
42.
Loder RT. The influence of diabetes mellitus on the healing of closed fractures. Clin Orthop Relat Res. 1988;232:210–6.PubMed
43.
Levin ME, Boisseau VC, Avioli LV. Effects of diabetes mellitus on bone mass in juvenile and adult-onset diabetes. N Engl J Med. 1976;294(5):241–5.PubMedCrossRef
44.
Verhaeghe J, van Herck E, Visser WJ, et al. Bone and mineral metabolism in BB rats with long-term diabetes. Decreased bone turnover and osteoporosis. Diabetes. 1990;39(4):477–82.PubMedCrossRef
45.
Lu H, Kraut D, Gerstenfeld LC, Graves DT. Diabetes interferes with the bone formation by affecting the expression of transcription factors that regulate osteoblast differentiation. Endocrinology. 2003;144(1):346–52.PubMedCrossRef
46.
Gandhi A, Beam HA, O'Connor JP, Parsons JR, Lin SS. The effects of local insulin delivery on diabetic fracture healing. Bone. 2005;37(4):482–90.PubMedCrossRef
47.
Ferron M, Wei J, Yoshizawa T, et al. Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell. 2010;142(2):296–308.PubMedCrossRefPubMedCentral
48.
Fulzele K, Riddle RC, DiGirolamo DJ, et al. Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition. Cell. 2010;142(2):309–19.PubMedCrossRefPubMedCentral
49.
Thrailkill K, Bunn RC, Lumpkin Jr C, et al. Loss of insulin receptor in osteoprogenitor cells impairs structural strength of bone. J Diabetes Res. 2014;2014:703589.PubMedCrossRefPubMedCentral
50.
Kawai M, Rosen CJ. The insulin-like growth factor system in bone: basic and clinical implications. Endocrinol Metab Clin N Am. 2012;41(2):323–33. vi.CrossRef
51.
Nakae J, Kido Y, Accili D. Distinct and overlapping functions of insulin and IGF-I receptors. Endocr Rev. 2001;22(6):818–35.PubMedCrossRef
52.
Bikle D, Majumdar S, Laib A, et al. The skeletal structure of insulin-like growth factor I-deficient mice. J Bone Miner Res. 2001;16(12):2320–9.PubMedCrossRef
53.
Zhao G, Monier-Faugere MC, Langub MC, et al. Targeted overexpression of insulin-like growth factor I to osteoblasts of transgenic mice: increased trabecular bone volume without increased osteoblast proliferation. Endocrinology. 2000;141(7):2674–82.PubMed
54.
Govoni KE, Wergedal JE, Florin L, Angel P, Baylink DJ, Mohan S. Conditional deletion of insulin-like growth factor-I in collagen type 1alpha2-expressing cells results in postnatal lethality and a dramatic reduction in bone accretion. Endocrinology. 2007;148(12):5706–15.PubMedCrossRefPubMedCentral
55.
Xian L, Wu X, Pang L, et al. Matrix IGF-1 maintains bone mass by activation of mTOR in mesenchymal stem cells. Nat Med. 2012;18(7):1095–101.
56.
Zhang M, Xuan S, Bouxsein ML, et al. Osteoblast-specific knockout of the insulin-like growth factor (IGF) receptor gene reveals an essential role of IGF signaling in bone matrix mineralization. J Biol Chem. 2002;277(46):44005–12.PubMedCrossRef
57.
Brabant G, von zur Muhlen A, Wuster C, et al. Serum insulin-like growth factor I reference values for an automated chemiluminescence immunoassay system: results from a multicenter study. Horm Res. 2003;60(2):53–60.PubMedCrossRef
58.
Seck T, Scheppach B, Scharla S, et al. Concentration of insulin-like growth factor (IGF)-I and -II in iliac crest bone matrix from pre- and postmenopausal women: relationship to age, menopause, bone turnover, bone volume, and circulating IGFs. J Clin Endocrinol Metab. 1998;83(7):2331–7.PubMed
59.
Cao JJ, Kurimoto P, Boudignon B, Rosen C, Lima F, Halloran BP. Aging impairs IGF-I receptor activation and induces skeletal resistance to IGF-I. J Bone Miner Res. 2007;22(8):1271–9.PubMedCrossRef
60.
Bikle DD, Sakata T, Leary C, et al. Insulin-like growth factor I is required for the anabolic actions of parathyroid hormone on mouse bone. J Bone Miner Res. 2002;17(9):1570–8.PubMedCrossRef
61.
Wang Y, Nishida S, Boudignon BM, et al. IGF-I receptor is required for the anabolic actions of parathyroid hormone on bone. J Bone Miner Res. 2007;22(9):1329–37.PubMedCrossRef
62.
Miyakoshi N, Kasukawa Y, Linkhart TA, Baylink DJ, Mohan S. Evidence that anabolic effects of PTH on bone require IGF-I in growing mice. Endocrinology. 2001;142(10):4349–56.PubMedCrossRef
Metadaten
Titel
Aerobic Glycolysis in Osteoblasts
verfasst von
Emel Esen
Fanxin Long
Publikationsdatum
01.12.2014
Verlag
Springer US
Erschienen in
Current Osteoporosis Reports / Ausgabe 4/2014
Print ISSN: 1544-1873
Elektronische ISSN: 1544-2241
DOI
https://doi.org/10.1007/s11914-014-0235-y

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