GPR48通过其他信号通路对骨吸收代谢作用的影响
除OPG／RANKL／RANK分子轴和CN／NFAT信号通路外，作为OPG／RANKL／RANK分子轴下游的PI3K／Akt、NF-κB和MAPK信号通路等在骨吸收代谢的调控过程中亦扮演着重要的角色。在本综述的前部分已提到GPR48同RANKL竞争性地与RANK结合影响其下游的相关信号通路，进而调控骨吸收代谢。既然GPR48与OPG／RANKL／RANK分子轴之间存在密切的影响关系，并且OPG／RANKL／RANK分子轴下游的PI3K／Akt、NF-κB和MAPK 3条信号通路在骨吸收代谢中也已被很多研究证实。因此，这3条信号通路在骨吸收代谢中的重要生物学作用可能与GPR48存在密切的调控作用。有研究已证实，当敲除小鼠GPR48后，骨吸收代谢明显增强，骨量和骨密度显著下降，而上述3条信号通路中相关细胞因子表达变化，在骨吸收代谢起着重要的调控作用。那么敲除GPR48后骨量和骨密度下降，可能是通过PI3K／Akt、NF-κB或者MAPK信号通路进而影响相关细胞因子表达，从而影响破骨细胞分化的产生；在功能发挥上，使得骨吸收代谢超过骨形成代谢，从而导致骨量和骨密度下降。目前，国内外有关GPR48通过以上3条信号通路进而调控骨吸收代谢的相关研究尚未见报道，生物学机制尚不明确，这将是以后GPR48和骨吸收代谢的研究方向之一。
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