Experimental Study on Nicotine-Nicotine acts directly on growth plate chondrocytes to delay enchondral ossification through the alpha7 homopentameric neuronal nicotinic acetylcholine receptor-

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We investigated the effect of nicotine on human growth plate chondrocytes, a major component of enchondral ossification. The chondrocytes were derived from extra human fingers. Both human and murine growth plate chondrocytes expressed alpha7 nicotinic acetylcholine receptor(nAChR), which constitutes functional homopentameric receptors. Nicotine inhibited matrix synthesis and hypertrophic differentiation in human growth plate chondrocytes in suspension culture in a concentration-dependent manner. Methyllycaconitine(MLA), a specific antagonist of alpha7 nAChR, reversed the inhibition of matrix synthesis and functional calcium influx by nicotine in human growth plate chondrocytes in vitro. In vivo, maternal nicotine exposure resulted in delayed skeletal growth of alpha7 nAChR+/+fetuses but not in alpha7 nAChR-/-fetuses, implying that skeletal growth retardation by nicotine is specifically mediated via fetal alpha7 nAChR. These results suggest that nicotine, from cigarette smoking, acts directly on growth plate chondrocytes to decrease matrix synthesis, suppress hypertrophic differentiation, and consequently to delay enchondral ossification via alpha7 nAChR, leading to delayed skeletal growth and delayed fracture repair or non-union.