nach oben

Erschienen in:

01.11.2010

The Expression of IL-6 by Osteoblasts Is Increased in Healthy Elderly Individuals: Stimulated Proliferation and Differentiation Are Unaffected by Age

verfasst von: Charlotte Grith Eriksen, Helene Olsen, Lise Bjerre Husted, Lotte Sørensen, Mette Carstens, Kjeld Søballe, Bente Lomholt Langdahl

Erschienen in: Calcified Tissue International | Ausgabe 5/2010

Einloggen, um Zugang zu erhalten

Abstract

Increasing age is associated with reduced bone mineral content and increased risk of fractures. This is caused by a relative insufficiency of osteoblasts compared with osteoclasts. We therefore wanted to examine the potential differences in proliferation, differentiation, and expression of cytokines between human osteoblasts (hOBs) obtained from young and elderly individuals. Cultures of hOBs were obtained from 11 elderly (73–85 years) and 15 young (21–27 years) healthy individuals. The cells were stimulated with hGH, IGF-I, hGH + IGF-I, and TGF-β1. Proliferation was evaluated by thymidine incorporation, and differentiation was evaluated by alkaline phosphatase, OPG, and PINP production. Expression of IL-6, TGF-β1, OPG, and RANKL was investigated using real-time PCR and three carefully selected housekeeping genes. Combined stimulation with hGH and IGF-I increased proliferation without differences between hOBs obtained from young and elderly individuals. hOBs from young individuals responded to stimulation with vitamin D with a more pronounced increase in alkaline phosphatase: 107 ± 17% vs. 43 ± 5%, P < 0.01. Stimulation with TGF-β1 decreased OPG production by hOBs from elderly individuals but not from young individuals, P < 0.05. hOBs from elderly individuals expressed significantly higher amounts of IL-6 mRNA (P < 0.05) and less OPG and TGF-β1 mRNA (P = 0.08 and P = 0.08, respectively) compared with hOBs from young individuals. In conclusion, hOBs from elderly individuals express more IL-6 mRNA and less OPG and TGF-β1 mRNA than hOBs from young individuals. This could partly explain the reduced bone mass and increased fracture risk seen in the elderly. hOBs from young and elderly individuals responded similarly to short-term stimulation of proliferation and differentiation.

Eriksen EF, Hodgson SF, Eastell R, Cedel SL, O’Fallon WM, Riggs BL (1990) Cancellous bone remodeling in type I (postmenopausal) osteoporosis: quantitative assessment of rates of formation, resorption, and bone loss at tissue and cellular levels. J Bone Miner Res 5:311–319CrossRefPubMed

Stenderup K, Justesen J, Clausen C, Kassem M (2003) Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells. Bone 33:919–926CrossRefPubMed

Abdallah BM, Haack-Sorensen M, Fink T, Kassem M (2006) Inhibition of osteoblast differentiation but not adipocyte differentiation of mesenchymal stem cells by sera obtained from aged females. Bone 39:181–188CrossRefPubMed

Manolagas SC (2000) Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev 21:115–137CrossRefPubMed

Pacifici R (1996) Estrogen, cytokines, and pathogenesis of postmenopausal osteoporosis. J Bone Miner Res 11:1043–1051CrossRefPubMed

Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT, Martin TJ (1999) Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev 20:345–357CrossRefPubMed

Hofbauer LC, Khosla S, Dunstan CR, Lacey DL, Boyle WJ, Riggs BL (2000) The roles of osteoprotegerin and osteoprotegerin ligand in the paracrine regulation of bone resorption. J Bone Miner Res 15:2–12CrossRefPubMed

Kurihara N, Civin C, Roodman GD (1991) Osteotropic factor responsiveness of highly purified populations of early and late precursors for human multinucleated cells expressing the osteoclast phenotype. J Bone Miner Res 6:257–261CrossRefPubMed

Roodman GD (1992) Interleukin-6: an osteotropic factor? J Bone Miner Res 7:475–478CrossRefPubMed

10.

Taguchi Y, Yamamoto M, Yamate T, Lin SC, Mocharla H, DeTogni P, Nakayama N, Boyce BF, Abe E, Manolagas SC (1998) Interleukin-6-type cytokines stimulate mesenchymal progenitor differentiation toward the osteoblastic lineage. Proc Assoc Am Physicians 110:559–574PubMed

11.

Bellido T, Borba VZ, Roberson P, Manolagas SC (1997) Activation of the Janus kinase/STAT (signal transducer and activator of transcription) signal transduction pathway by interleukin-6-type cytokines promotes osteoblast differentiation. Endocrinology 138:3666–3676CrossRefPubMed

12.

Abrahamsen B, Bonnevie-Nielsen V, Ebbesen EN, Gram J, Beck-Nielsen H (2000) Cytokines and bone loss in a 5-year longitudinal study–hormone replacement therapy suppresses serum soluble interleukin-6 receptor and increases interleukin-1-receptor antagonist: the Danish Osteoporosis Prevention Study. J Bone Miner Res 15:1545–1554CrossRefPubMed

13.

Oursler MJ (1994) Osteoclast synthesis and secretion and activation of latent transforming growth factor beta. J Bone Miner Res 9:443–452CrossRefPubMed

14.

Chenu C, Pfeilschifter J, Mundy GR, Roodman GD (1988) Transforming growth factor beta inhibits formation of osteoclast-like cells in long-term human marrow cultures. Proc Natl Acad Sci USA 85:5683–5687CrossRefPubMed

15.

Shinar DM, Rodan GA (1990) Biphasic effects of transforming growth factor-beta on the production of osteoclast-like cells in mouse bone marrow cultures: the role of prostaglandins in the generation of these cells. Endocrinology 126:3153–3158CrossRefPubMed

16.

Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian YX, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle WJ (1998) Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93:165–176CrossRefPubMed

17.

Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, Tomoyasu A, Yano K, Goto M, Murakami A, Tsuda E, Morinaga T, Higashio K, Udagawa N, Takahashi N, Suda T (1998) Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci USA 95:3597–3602CrossRefPubMed

18.

Akatsu T, Murakami T, Nishikawa M, Ono K, Shinomiya N, Tsuda E, Mochizuki S, Yamaguchi K, Kinosaki M, Higashio K, Yamamoto M, Motoyoshi K, Nagata N (1998) Osteoclastogenesis inhibitory factor suppresses osteoclast survival by interfering in the interaction of stromal cells with osteoclast. Biochem Biophys Res Commun 250:229–234CrossRefPubMed

19.

Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Goto M, Mochizuki SI, Tsuda E, Morinaga T, Udagawa N, Takahashi N, Suda T, Higashio K (1999) A novel molecular mechanism modulating osteoclast differentiation and function. Bone 25:109–113CrossRefPubMed

20.

Yasuda H, Shima N, Nakagawa N, Mochizuki SI, Yano K, Fujise N, Sato Y, Goto M, Yamaguchi K, Kuriyama M, Kanno T, Murakami A, Tsuda E, Morinaga T, Higashio K (1998) Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. Endocrinology 139:1329–1337CrossRefPubMed

21.

Emery JG, McDonnell P, Burke MB, Deen KC, Lyn S, Silverman C, Dul E, Appelbaum ER, Eichman C, DiPrinzio R, Dodds RA, James IE, Rosenberg M, Lee JC, Young PR (1998) Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. J Biol Chem 273:14363–14367CrossRefPubMed

22.

Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Luthy R, Nguyen HQ, Wooden S, Bennett L, Boone T, Shimamoto G, DeRose M, Elliott R, Colombero A, Tan HL, Trail G, Sullivan J, Davy E, Bucay N, Renshaw-Gegg L, Hughes TM, Hill D, Pattison W, Campbell P, Boyle WJ (1997) Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89:309–319CrossRefPubMed

23.

Bu R, Borysenko CW, Li Y, Cao L, Sabokbar A, Blair HC (2003) Expression and function of TNF-family proteins and receptors in human osteoblasts. Bone 33:760–770CrossRefPubMed

24.

Rubin J, Ackert-Bicknell CL, Zhu L, Fan X, Murphy TC, Nanes MS, Marcus R, Holloway L, Beamer WG, Rosen CJ (2002) IGF-I regulates osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand in vitro and OPG in vivo. J Clin Endocrinol Metab 87:4273–4279CrossRefPubMed

25.

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 140:3552–3561CrossRefPubMed

26.

Vidal NO, Brandstrom H, Jonsson KB, Ohlsson C (1998) Osteoprotegerin mRNA is expressed in primary human osteoblast-like cells: down-regulation by glucocorticoids. J Endocrinol 159:191–195CrossRefPubMed

27.

Brandstrom H, Jonsson KB, Vidal O, Ljunghall S, Ohlsson C, Ljunggren O (1998) Tumor necrosis factor-alpha and -beta upregulate the levels of osteoprotegerin mRNA in human osteosarcoma MG-63 cells. Biochem Biophys Res Commun 248:454–457CrossRefPubMed

28.

Tsukii K, Shima N, Mochizuki S, Yamaguchi K, Kinosaki M, Yano K, Shibata O, Udagawa N, Yasuda H, Suda T, Higashio K (1998) Osteoclast differentiation factor mediates an essential signal for bone resorption induced by 1alpha, 25-dihydroxyvitamin D3, prostaglandin E2, or parathyroid hormone in the microenvironment of bone. Biochem Biophys Res Commun 246:337–341CrossRefPubMed

29.

Kassem M, Mosekilde L, Eriksen EF (1993) 1,25-Dihydroxyvitamin D3 potentiates fluoride-stimulated collagen type I production in cultures of human bone marrow stromal osteoblast-like cells. J Bone Miner Res 8:1453–1458CrossRefPubMed

30.

Kassem M, Kveiborg M, Eriksen EF (2000) Production and action of transforming growth factor-beta in human osteoblast cultures: dependence on cell differentiation and modulation by calcitriol. Eur J Clin Invest 30:429–437CrossRefPubMed

31.

Langdahl BL, Kassem M, Moller MK, Eriksen EF (1998) The effects of IGF-I and IGF-II on proliferation and differentiation of human osteoblasts and interactions with growth hormone. Eur J Clin Invest 28:176–183CrossRefPubMed

32.

Kassem M, Mosekilde L, Eriksen EF (1993) Effects of triiodothyronine on DNA synthesis and differentiation markers of normal human osteoblast-like cells in vitro. Biochem Mol Biol Int 30:779–788PubMed

33.

Kassem M, Risteli L, Mosekilde L, Melsen F, Eriksen EF (1991) Formation of osteoblast-like cells from human mononuclear bone marrow cultures. APMIS 99:269–274CrossRefPubMed

34.

Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159CrossRefPubMed

35.

Chomczynski P (1993) A reagent for the single-step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples. Biotechniques 15:532–537PubMed

36.

Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F (2002) Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 3:RESEARCH0034

37.

Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−ΔΔC(T)) method. Methods 25:402–408CrossRefPubMed

38.

Kassem M, Mosekilde L, Eriksen EF (1994) Growth hormone stimulates proliferation of normal human bone marrow stromal osteoblast precursor cells in vitro. Growth Regul 4:131–135PubMed

39.

Robey PG, Young MF, Flanders KC, Roche NS, Kondaiah P, Reddi AH, Termine JD, Sporn MB, Roberts AB (1987) Osteoblasts synthesize and respond to transforming growth factor-type beta (TGF-beta) in vitro. J Cell Biol 105:457–463CrossRefPubMed

40.

Noda M, Rodan GA (1987) Type beta transforming growth factor (TGF beta) regulation of alkaline phosphatase expression and other phenotype-related mRNAs in osteoblastic rat osteosarcoma cells. J Cell Physiol 133:426–437CrossRefPubMed

41.

Matsumoto T, Igarashi C, Takeuchi Y, Harada S, Kikuchi T, Yamato H, Ogata E (1991) Stimulation by 1,25-dihydroxyvitamin D3 of in vitro mineralization induced by osteoblast-like MC3T3–E1 cells. Bone 12:27–32CrossRefPubMed

42.

Canalis E (1993) Insulin like growth factors and the local regulation of bone formation. Bone 14:273–276CrossRefPubMed

43.

Thomas T, Gori F, Spelsberg TC, Khosla S, Riggs BL, Conover CA (1999) Response of bipotential human marrow stromal cells to insulin-like growth factors: effect on binding protein production, proliferation, and commitment to osteoblasts and adipocytes. Endocrinology 140:5036–5044CrossRefPubMed

44.

Suda T, Udagawa N, Nakamura I, Miyaura C, Takahashi N (1995) Modulation of osteoclast differentiation by local factors. Bone Suppl 2:87–91CrossRef

45.

Ralston SH (1994) Analysis of gene expression in human bone biopsies by polymerase chain reaction: evidence for enhanced cytokine expression in postmenopausal osteoporosis. J Bone Miner Res 9:883–890CrossRefPubMed

46.

Abdallah BM, Stilgren LS, Nissen N, Kassem M, Jorgensen HR, Abrahamsen B (2005) Increased RANKL/OPG mRNA ratio in iliac bone biopsies from women with hip fractures. Calcif Tissue Int 76:90–97CrossRefPubMed

47.

Eastell R, Delmas PD, Hodgson SF, Eriksen EF, Mann KG, Riggs BL (1988) Bone formation rate in older normal women: concurrent assessment with bone histomorphometry, calcium kinetics, and biochemical markers. J Clin Endocrinol Metab 67:741–748CrossRefPubMed

48.

Horner A, Kemp P, Summers C, Bord S, Bishop NJ, Kelsall AW, Coleman N, Compston JE (1998) Expression and distribution of transforming growth factor-beta isoforms and their signaling receptors in growing human bone. Bone 23:95–102CrossRefPubMed

49.

Hering S, Isken E, Knabbe C, Janott J, Jost C, Pommer A, Muhr G, Schatz H, Pfeiffer AF (2001) TGFbeta1 and TGFbeta2 mRNA and protein expression in human bone samples. Exp Clin Endocrinol Diabetes 109:217–226CrossRefPubMed

50.

Bonewald LF, Mundy GR (1990) Role of transforming growth factor-beta in bone remodeling. Clin Orthop Relat Res 250:261–276PubMed

51.

Bonewald LF (1999) Regulation and regulatory activities of transforming growth factor beta. Crit Rev Eukaryot Gene Expr 9:33–44PubMed

52.

Nakashima T, Kobayashi Y, Yamasaki S, Kawakami A, Eguchi K, Sasaki H, Sakai H (2000) Protein expression and functional difference of membrane-bound and soluble receptor activator of NF-kappaB ligand: modulation of the expression by osteotropic factors and cytokines. Biochem Biophys Res Commun 275:768–775CrossRefPubMed

53.

Eskola JU, Hamalainen M, Nanto V, Rajamaki A, Dahlen P, Iitia A, Siitari H (1994) Detection of Philadelphia chromosome using PCR and europium-labeled DNA probes. Clin Biochem 27:373–379CrossRefPubMed

54.

Bustin SA (2000) Absolute quantification of mRNA using real-time reverse transcription polymerase chain reaction assays. J Mol Endocrinol 25:169–193CrossRefPubMed

55.

Suzuki T, Higgins PJ, Crawford DR (2000) Control selection for RNA quantitation. Biotechniques 29:332–337PubMed

56.

Thellin O, Zorzi W, Lakaye B, De Borman B, Coumans B, Hennen G, Grisar T, Igout A, Heinen E (1999) Housekeeping genes as internal standards: use and limits. J Biotechnol 75:291–295CrossRefPubMed

57.

Justesen J, Stenderup K, Eriksen EF, Kassem M (2002) Maintenance of osteoblastic and adipocytic differentiation potential with age and osteoporosis in human marrow stromal cell cultures. Calcif Tissue Int 71:36–44CrossRefPubMed

58.

Stenderup K, Rosada C, Justesen J, Al Soubky T, Dagnaes-Hansen F, Kassem M (2004) Aged human bone marrow stromal cells maintaining bone forming capacity in vivo evaluated using an improved method of visualization. Biogerontology 5:107–118CrossRefPubMed

59.

Stenderup K, Justesen J, Eriksen EF, Rattan SI, Kassem M (2001) Number and proliferative capacity of osteogenic stem cells are maintained during aging and in patients with osteoporosis. J Bone Miner Res 16:1120–1129CrossRefPubMed

60.

Balla B, Kosa JP, Kiss J, Borsy A, Podani J, Takacs I, Lazary A, Nagy Z, Bacsi K, Speer G, Orosz L, Lakatos P (2008) Different gene expression patterns in the bone tissue of aging postmenopausal osteoporotic and non-osteoporotic women. Calcif Tissue Int 82:12–26CrossRefPubMed

Titel: The Expression of IL-6 by Osteoblasts Is Increased in Healthy Elderly Individuals: Stimulated Proliferation and Differentiation Are Unaffected by Age
verfasst von: Charlotte Grith Eriksen
Helene Olsen
Lise Bjerre Husted
Lotte Sørensen
Mette Carstens
Kjeld Søballe
Bente Lomholt Langdahl
Publikationsdatum: 01.11.2010
Verlag: Springer-Verlag
Erschienen in: Calcified Tissue International / Ausgabe 5/2010
Print ISSN: 0171-967X
Elektronische ISSN: 1432-0827
DOI: https://doi.org/10.1007/s00223-010-9412-x

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

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

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

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.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

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

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 5/2010

Effects of Smoking on Severity of Disease in Primary Hyperparathyroidism

Intermittent PTH1–34 Causes DNA and Chromosome Breaks in Osteoblastic and Nonosteoblastic Cells

Contribution of Mineral to Bone Structural Behavior and Tissue Mechanical Properties

Osteoporosis Therapies: Evidence from Health-Care Databases and Observational Population Studies

Potential of Resveratrol Analogues as Antagonists of Osteoclasts and Promoters of Osteoblasts