IADR Abstract Archives
Extracellular nucleotides in muscle-bone crosstalk at the masticatory system
Objectives: Molecular basis of muscle-bone crosstalk is totally unknown at the masticatory system. We have previously demonstrated that the extracellular ATP (eATP) is a relevant signalling molecule that releases after limb muscles contraction and controls muscle plasticity. Moreover, eATP has been widely related to bone cells activation and differentiation. The aim of this work is to determine if extracellular ATP signalling pathway components are expressed at the masticatory system and if they control muscle plasticity and bone remodelling in pathophysiological conditions.
Methods: In male adult mice, expression of P2Y/P2X nucleotide receptors was assessed in masticatory system. ATP release from masseter muscles evoked by electrical stimulation (ES) was performed. IL-1β/IL-6 expression and release, and its dependence on eATP was addressed. Changes in masseter muscle phenotype and gene expression after soft-diet feeding or botulinum toxin type A (BoNTA) injection was measured. RANKL expression and bone microstructure parameters in mandible condyle were quantitated.
Results: Masticatory muscles (masseter, digastric), as well as mandible and maxilla bones, expressed several P2Y/P2X receptor subtypes. ES of masseter muscles released ATP through pannexin-1 hemichannels, that activated P2Y/P2X receptors increasing expression and secretion of IL-1β/IL-6. A soft diet induced masseter muscle atrophy, that increased basal levels of IL-1β/IL-6, as well as P2Y2 receptor and pannexin 1. Masseter muscle paralysis evoked by BoNTA injection induced muscle atrophy, with a significant bone loss in mandible condyle. An early increase in IL-1β/IL-6 was observed in masseter muscle, as well as an increase in RANKL in mandible condyle, 2d after BoNTA injection.
Conclusions: Masticatory muscles have a functional ATP signalling pathway. Changes in masticatory activity or muscle function, could induce bone remodelling by eATP itself or by myokines (IL-1β/IL-6) released in response to eATP. Unveiling this molecular mechanism could provide insights into the coordinated muscle-bone response to environmental demands in pathophysiological situations.
Methods: In male adult mice, expression of P2Y/P2X nucleotide receptors was assessed in masticatory system. ATP release from masseter muscles evoked by electrical stimulation (ES) was performed. IL-1β/IL-6 expression and release, and its dependence on eATP was addressed. Changes in masseter muscle phenotype and gene expression after soft-diet feeding or botulinum toxin type A (BoNTA) injection was measured. RANKL expression and bone microstructure parameters in mandible condyle were quantitated.
Results: Masticatory muscles (masseter, digastric), as well as mandible and maxilla bones, expressed several P2Y/P2X receptor subtypes. ES of masseter muscles released ATP through pannexin-1 hemichannels, that activated P2Y/P2X receptors increasing expression and secretion of IL-1β/IL-6. A soft diet induced masseter muscle atrophy, that increased basal levels of IL-1β/IL-6, as well as P2Y2 receptor and pannexin 1. Masseter muscle paralysis evoked by BoNTA injection induced muscle atrophy, with a significant bone loss in mandible condyle. An early increase in IL-1β/IL-6 was observed in masseter muscle, as well as an increase in RANKL in mandible condyle, 2d after BoNTA injection.
Conclusions: Masticatory muscles have a functional ATP signalling pathway. Changes in masticatory activity or muscle function, could induce bone remodelling by eATP itself or by myokines (IL-1β/IL-6) released in response to eATP. Unveiling this molecular mechanism could provide insights into the coordinated muscle-bone response to environmental demands in pathophysiological situations.