摘要
Connexins和Pannexins在骨细胞和成骨细分化、细胞内信号转导、维持骨平衡以及骨再生中起着重要作用.本文就Connexins介导的缝隙连接及Pannexins介导的半通道在骨中的研究进展和局限性进行综述.目前的研究已经阐明这些分子以缝隙连接的形式或是独立的半通道的形式传递外界刺激到骨骼系统.然而,对于Connexins和Pannexins家族成员在骨发育和骨稳态中其他类型细胞如成骨细胞前体、骨髓间充质干细胞等,在维持正常生物学行为中的作用所知甚少.此外,目前Connexins家族中研究最多的成员是Connexin43(Cx43),其他成员在骨骼发育中的作用与机制尚缺乏研究.基因编辑动物模型为研究Connexins和Pannexins在骨骼系统中的作用提供了基本的信息,但是Connexins和Pannexins之间的异同仍然有待发现.将一种特定功能定位于Connexins或Pannexins对骨作用刺激和骨骼疾病的影响仍然是一个难题,其困扰是通道之间药理选择性重叠、其他亚型的补偿、评估通道功能的方法差异,以及与转基因小鼠模型相关的基因改变.因此,需要更好的工具和研究途径来了解这些通道在骨和软骨中的作用.未来研究的一个基本任务是找到特定的可以调节Connexins或Pannexins亚型的化合物,使其能够作为药物制剂治疗骨骼疾病,为改善骨骼健康、治疗骨骼系统的疾病开发新的治疗策略提供可能.
Connexins and Pannexins play important roles in osteocytes and osteoblasts differentiation,intracellular signal transduction,maintenance of bone balance,and bone regeneration.This article reviews the progress and limitations of Connexins-mediated gap junctions and Pannexins mediated hemichannel in bone.Current research has shown that these molecules,in the form of gap junctions or separate hemichannels,deliver external stimuli to the skeletal system.However,little is known about the role of other cell types in bone development and homeostasis,such as pre-osteoblasts and bone marrow mesenchymal stem cells,in maintaining normality.In addition,at present,the most well-studied member of the Connexins family is Connexin43(Cx43),while the roles and mechanisms of other members in bone development are still behind the veil.Gene-edited animal models provide basic information on the role of Connexins and Pannexins in the skeletal system,but the similarities and differences between Connexins and Pannexins remain to be discovered.Targeting a specific function of Connexins or Pannexins for bone stimulation and bone disease remains a challenge,with pharmacological selective overlap between channels,compensation of other subtypes,differences in methods for assessing channel function,and genetic changes associated with transgenic mouse models.Therefore,better tools and research pathways are needed to understand the role of these pathways in bone and cartilage.An essential task for future research will be to identify specific compounds that regulate Connexins or Pannexins subtypes to enable them to be used as pharmaceutical agents in the treatment of bone diseases,providing the possibility to develop new therapeutic strategies for improving bone health and treating diseases of the skeletal system.
作者
刘文静
张德茂
周学东
谢静
LIU Wen-jing;ZHANG De-mao;ZHOU Xue-dong;XIE Jing(State Key Laboratory of Oral Diseases,National Clinical Research Center for Oral Diseases,West China Hospital of Stomatology,Sichuan University,Chengdu 610041,China)
出处
《四川大学学报（医学版）》
CAS
CSCD
北大核心
2020年第6期771-776,共6页
Journal of Sichuan University(Medical Sciences)
基金
国家自然科学基金(No.81600840、No.81771047)资助。
