EFFECTS OF CLENBUTEROL ON BONE BY INCREASED RANKL FOR OSTEOCLAST

Abstract

Clenbuterol is one of the beta-2 adrenergic receptor agonists with powerful muscle anabolic and lipolytic effects and is prohibited to use as doping drug for athletes. Since previously we have reported that clenbuterol induced the muscular hypertrophy but inhibited the longitudinal growth of bones in young male rats (MSSE 34(2):267–273, 2002). However, the mechanism of the inhibitory growth effect on bone was not explained yet. Furthermore, we suggested that clenbuterol might decrease the lactate metabolism by the decreased expression of lactate transporter (MCT1 and MCT4) in muscles (JAP 91(1), 85–90, 2001). The effect of blood lactate produced by exercise or clenbuterol on bone was not clear yet. PURPOSE The purpose of this study was to examine the effects of clenbuterol on the osteogenetic system in vitro. METHOD In the present study, the effect of clenbuterol was examined using reverse-transcription polymerase chain reaction (RT-PCR) analysis of the clonal stromal cells (ST2 cells) derived from mouse bone marrow to osteoblast-like cells. The ST2 cell was treated with 10−5 ∼ 10−1M clenbuterol or lactate. We examined the expression of two types of lactate transporters (MCT1 and MCT4), receptor activator of nuclear factor-kappaB ligand (RANKL), and alkaline phosphatase (ALP), a cellular differentiation marker, in cells with osteogenetic potential. RESULT Northern blot analysis showed the clenbuterol induced no change of the expression of mRNAs of MCT1, MCT4, and ALP with compare to control. However, it induced rapidly increase of the mRNA of RANKL which was positive regulators in osteoclast formation. CONCLUSION These results indicated that clenbuterol might induce the promotion of osteoclast formation directly via beta-2 receptor. In part, it may explain the inhibited longitudinal growth of bones by clenbuterol treatment in young rats.