title: L-carnitine and isovaleryl L-carnitine fumarate positively affect human osteoblast proliferation and differentiation in vitro.
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.
authors.affiliation: Department of Human Anatomy and Histology, University of Bari, Bari, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Colucci
authors.forename: G
authors.initials: G
authors.lastname: Mori
authors.forename: S
authors.initials: S
authors.lastname: Vaira
authors.forename: G
authors.initials: G
authors.lastname: Brunetti
authors.forename: G
authors.initials: G
authors.lastname: Greco
authors.forename: L
authors.initials: L
authors.lastname: Mancini
authors.forename: G M
authors.initials: GM
authors.lastname: Simone
authors.forename: F
authors.initials: F
authors.lastname: Sardelli
authors.forename: A
authors.initials: A
authors.lastname: Koverech
authors.forename: A
authors.initials: A
authors.lastname: Zallone
authors.forename: M
authors.initials: M
authors.lastname: Grano
mesh_terms: D000469:Alkaline Phosphatase / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D002113:Calcification, Physiologic / Q000187:drug effects; D002331:Carnitine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects*; D015675:Osteocalcin / Q000187:drug effects / Q000378:metabolism; D053495:Osteopontin; D017451:Receptors, Somatomedin / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000187:drug effects / Q000378:metabolism; D013002:Somatomedins / Q000187:drug effects / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D017451:Receptors, Somatomedin; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D013002:Somatomedins; D015675:Osteocalcin; D053495:Osteopontin; D000469:Alkaline Phosphatase; D002331:Carnitine