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L-Carnitine and Isovaleryl L-Carnitine Fumarate Positively Affect Human Osteoblast Proliferation and Differentiation In Vitro

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Abstract

Age-related bone loss is characterized by decreased osteoblast activity, possibly related to the reduction of energy production. Carnitine promotes energy availability and its concentration declines with age; Therefore, two Carnitine derivatives, L-carnitine fumarate (LC) and isovaleryl L-carnitine fumarate (Iso-V-LC), have been tested on several parameters of human osteoblasts in vitro. Both compounds significantly increased osteoblast activity, but the new compound Iso-V-LC was more efficient than LC at lower concentrations. They both significantly enhanced cell proliferation, [3H]-proline incorporation and the expression of collagen type I (COLLI), and the bone sialoproteins (BSPs) and osteopontin (OPN). The percentage of alkaline phosphatase (ALP)–positive cells and the secretion of osteocalcin were not modified by LC and Iso-V-LC. Both molecules increased the formation of mineralized nodules, but Iso-V-LC reached the maximum effect at a concentration 10-fold lower than that of LC. Furthermore, we showed that insulin-like growth factor (IGF)-I and IGF-II mRNA levels were not modified by the treatment. However, the two compounds induced an increase of insulin-like growth factor binding protein (IGFBP)-3 and a decrease of IGFBP-5 in both osteoblast lysates and the extracellular matrix (ECM). In conclusion these data suggest that carnitine and, in particular, its new derivative, Iso-V-LC supplementation in the elderly may stimulate osteoblast activity and decrease age-related bone loss.

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References

  1. C Schimd T Steiner ER Froesch (1982) ArticleTitleInsulin-like growth factor I supports differentiation of cultured osteoblast-like cells FEBS Lett 148 31–34 Occurrence Handle10.1016/0014-5793(82)81236-2 Occurrence Handle6293873

    Article  PubMed  Google Scholar 

  2. C Schmid T Steiner ER Froesch (1983) ArticleTitleInsulin-like growth factor stimulates synthesis of nucleic acids and glycogen in cultured calvaria cells Calcif Tissue Int 35 578–585 Occurrence Handle6193851

    PubMed  Google Scholar 

  3. G Adamek R Felix HL Guenther H Fleisch (1987) ArticleTitleFatty acid oxidation in bone tissue and bone cells in culture Biochem J 242 129–137

    Google Scholar 

  4. PR Borum (1980) Regulation of carnitine concentration in plasma RA Frenkel JD McGarry (Eds) Carnitine biosynthesis, metabolism and functions Academic Press New York 115–126

    Google Scholar 

  5. F Maccari A Arseni P Chiodi MT Ramacii L Angelucci (1990) ArticleTitleLevels of carnitines in brain and other tissues of rats of different ages: effect of acetyl-itine administration Exp Gerontol 25 127–134 Occurrence Handle10.1016/0531-5565(90)90043-2 Occurrence Handle2369927

    Article  PubMed  Google Scholar 

  6. M Costell JE O’Connor S Grisolia (1989) ArticleTitleAge-dependent decrease of carnitine content in muscle of mice and humans Biochem Biophys Res Commun 161 1135–1143 Occurrence Handle10.1016/0006-291X(89)91360-0 Occurrence Handle2742580

    Article  PubMed  Google Scholar 

  7. M Costell S Grisolia (1993) ArticleTitleEffect of carnitine feeding on the levels of heart and skeletal muscle carnitine of elderly mice FEBS Lett 315 43–46 Occurrence Handle10.1016/0014-5793(93)81129-N Occurrence Handle8416809

    Article  PubMed  Google Scholar 

  8. KM Chiu ET Keller TD Crenshaw S Gravenstein (1999) ArticleTitleCarnitine and dehydroepiandrosterone sulphate induced protein synthesis in porcine osteoblast-like cells Calcif Tissue Int 64 527–533 Occurrence Handle10.1007/s002239900644 Occurrence Handle10341026

    Article  PubMed  Google Scholar 

  9. Canalis E (1994) Insulin-like growth factor, an autocrine regulator of skeletal cells. In: insulin-like growth factor and their regulatory proteins. Elsevier, Amsterdam, p 307

  10. S Mohan DJ Baylink (1996) ArticleTitleInsulin-like growth factor system components and the coupling of bone formation to resorption Horm Res 45 59–62

    Google Scholar 

  11. CJ Rosen LR Donahue (1998) ArticleTitleInsulin-like growth factors and bone: the osteoporosis connection revisited Proc Soc Exp Biol Med 219 1–7 Occurrence Handle9751217

    PubMed  Google Scholar 

  12. KB Jonsson S Ljunghall O Karlstom AG Johansson H Mallmin O Ljunggren (1993) ArticleTitleInsulin-like growth factor I enhances the formation of type I collagen in hydrocortisone-treated human osteoblasts Biosci Rep 13 297–302 Occurrence Handle10.1007/BF01137966 Occurrence Handle8142615

    Article  PubMed  Google Scholar 

  13. V Gangji S Rydziel B Gabbitas E Canalis (1998) ArticleTitleInsulin-like growth factor II promoter expression in cultured rodent osteoblasts and adult rat bone Endocrinology 139 2287–2292 Occurrence Handle10.1210/en.139.5.2287 Occurrence Handle9564836

    Article  PubMed  Google Scholar 

  14. S Shimasaki N Ling (1991) ArticleTitleIdentification and molecular characterization of insulin-like growth factor binding proteins (IGFBP-1,-2, -3, -5, and -6) Prog Growth Factor Res 3 243–266 Occurrence Handle10.1016/0955-2235(91)90003-M Occurrence Handle1725860

    Article  PubMed  Google Scholar 

  15. JHM Feyen DB Evans C Binkert GF Heinrich S Geisse HP Kocher (1991) ArticleTitleRecombinant human [Cys281]insulin-like growth factor-binding protein 2 inhibits both basal and insulin-like growth factor I-stimulated proliferation and collagen synthesis in fetal rat calvariae J Biol Chem 266 19469–19474 Occurrence Handle1717466

    PubMed  Google Scholar 

  16. M Ernst GA Rodan (1990) ArticleTitleIncreased activity of insulin-like growth factor (IGF) in osteoblastic cells in the presence of growth hormone (GH): positive correlation with the presence of the GH-induced IGF-binding protein BP-3 Endocrinology 127 807–814 Occurrence Handle2164921

    PubMed  Google Scholar 

  17. S Mohan CM Bautista J Wergedal DJ Baylink (1989) ArticleTitleIsolation of an inhibitory insulin-like growth factor (IGF) binding protein from bone cell-conditioned medium: a potential local regulator of IGF action Proc Natl Acad Sci USA 86 8338–8342 Occurrence Handle2479022

    PubMed  Google Scholar 

  18. D LaTour S Mohan TA Linkhart DJ Baylink DD Strong (1990) ArticleTitleInhibitory insulin-like growth factor-binding protein: cloning, complete sequence, and physiological regulation Mol Endocrinol 4 1806–1814 Occurrence Handle1707125

    PubMed  Google Scholar 

  19. MC Kiefer C Schmid M Waldvogel I Schlapfer E Futo FR Masiarz K Green PJ Barr J Zapf (1992) ArticleTitleCharacterization of recombinant human insulin-like growth factor binding proteins 4, 5, and 6 produced in yeast J Biol Chem 267 12692–12699 Occurrence Handle1377672

    PubMed  Google Scholar 

  20. M Kassem R Okazaki D Leon ParticleDe SA Harris JA Robinson TC Spelsberg CA Conover BL Riggs (1996) ArticleTitlePotential mechanism of estrogen-mediated decrease in bone formation: estrogen increases production of inhibitory insulin-like growth factor-binding protein-4 Proc Assoc Am Physicians 108 155–164 Occurrence Handle8705735

    PubMed  Google Scholar 

  21. CA Conover MC Kiefer (1993) ArticleTitleRegulation and biological effect of endogenous insulin-like growth factor binding protein-5 in human osteoblastic cells J Clin Endocrinol Metab 76 1153–1159 Occurrence Handle10.1210/jc.76.5.1153 Occurrence Handle7684391

    Article  PubMed  Google Scholar 

  22. PG Gehron-Robey JD Termine (1985) ArticleTitleHuman bone cells in vitro Calcif Tissue Int 37 453–460 Occurrence Handle2998572

    PubMed  Google Scholar 

  23. BS Knudsen PC Harpel RL Nachman (1987) ArticleTitlePlasminogen activator inhibitor is associated with the extracellular matrix of cultured bovine smooth muscle cells J Clin Invest 80 1082–1089 Occurrence Handle3116043

    PubMed  Google Scholar 

  24. SL Cheng CF Lai SD Blystone LV Avioli (2001) ArticleTitleBone mineralization and osteoblast differentiation are negatively modulated by integrin alpha(v)beta 3 J Bone Miner Res 16 277–288 Occurrence Handle11204428

    PubMed  Google Scholar 

  25. N Pischon LM Darbois AH Palamakumbura E Kessler PC Trackman (2004) ArticleTitleRegulation of collagen deposition and lysyl oxidase by tumor necrosis factor-alpha in osteoblasts J Biol Chem 279 30060–30065 Occurrence Handle10.1074/jbc.M404208200 Occurrence Handle15138266

    Article  PubMed  Google Scholar 

Download references

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Authors and Affiliations

  1. Department of Human Anatomy and Histology, University of Bari, Bari, Italy

    S. Colucci, G. Mori, S. Vaira, G. Brunetti, G. Greco, L. Mancini, G. M. Simone, A. Zallone & M. Grano

  2. Department Unit Carnitine, Sigma-tau, Roma, Italy

    F. Sardelli & A. Koverech

Authors
  1. S. Colucci
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  2. G. Mori
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  3. S. Vaira
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  4. G. Brunetti
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  5. G. Greco
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  6. L. Mancini
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  7. G. M. Simone
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  8. F. Sardelli
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  9. A. Koverech
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  10. A. Zallone
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  11. M. Grano
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Correspondence to M. Grano.

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Colucci, S., Mori, G., Vaira, S. et al. L-Carnitine and Isovaleryl L-Carnitine Fumarate Positively Affect Human Osteoblast Proliferation and Differentiation In Vitro. Calcif Tissue Int 76, 458–465 (2005). https://doi.org/10.1007/s00223-004-0147-4

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  • DOI: https://doi.org/10.1007/s00223-004-0147-4

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