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.

L-carnitine affects osteoblast differentiation in NIH3T3 fibroblasts by the IGF-1/PI3K/Akt signalling pathway

“…Some studies suggest that LC promoted osteoblast proliferation and differentiation in vitro (43,44), while other studies indicated that LC inhibited proliferation in VSMCs (45). In this study, we found that the 10 μM LC positively affected osteoblast proliferation, but the higher concentration of LC (100 μM) slightly decreased osteoblast proliferation compared with the control.…”

“…Studies indicated that cells of the osteoblastic lineage generate 40% to 80% of their energy demands through fatty acid β-oxidation (14). It has also been demonstrated that LC could protect osteoblastic cells from apoptosis (15,16), increased metabolic activity and protein production of porcine osteoblast-like cells (17), as well as affected osteoblastic activity (15).…”

Current, new and future treatments of osteoporosis

“…Formerly it was shown that these two compounds stimulate osteoblasts proliferation and differentiation by co-operation of insulinlike growth factors (IGFs) [129]. Also in osteoporotic pregnant mice Iso-V-LC and to a lesser extent LC accelerated bone recovery after a hypocalcemic diet [130].…”

The possible role of L-carnitine on the skeletal muscle of ovariectomized rats

“…Using an aging ovariectomized rat model they found supplementation of L-carnitine can influence bone density and slow the rate of bone turnover by slowing bone loss and improving bone microstructural properties through decreasing bone turnover (Hooshmand et al 2008). Also, Colucci et al (2005) used an in vitro model to suggest that carnitine supplementation in the elderly may stimulate osteoblast activity and decrease age-related bone loss. The apoptotic changes seen in the OVX rats' myofibers were hardly detected in L-carnitine treated group.…”