Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy.
Department of Human Sciences and Quality of Life Promotion, San Raffaele Roma Open University, 00166 Rome, Italy.
Int J Mol Sci. 2023 Feb 19;24(4):4156. doi: 10.3390/ijms24044156.
Gap junctions (GJs) formed by connexins (Cxs) play an important role in the intercellular communication within most body tissues. In this paper, we focus on GJs and Cxs present in skeletal tissues. Cx43 is the most expressed connexin, participating in the formation of both GJs for intercellular communication and hemichannels (HCs) for communication with the external environment. Through GJs in long dendritic-like cytoplasmic processes, osteocytes embedded in deep lacunae are able to form a functional syncytium not only with neighboring osteocytes but also with bone cells located at the bone surface, despite the surrounding mineralized matrix. The functional syncytium allows a coordinated cell activity through the wide propagation of calcium waves, nutrients and anabolic and/or catabolic factors. Acting as mechanosensors, osteocytes are able to transduce mechanical stimuli into biological signals that spread through the syncytium to orchestrate bone remodeling. The fundamental role of Cxs and GJs is confirmed by a plethora of investigations that have highlighted how up- and downregulation of Cxs and GJs critically influence skeletal development and cartilage functions. A better knowledge of GJ and Cx mechanisms in physiological and pathological conditions might help in developing therapeutic approaches aimed at the treatment of human skeletal system disorders.
间隙连接（GJ）由连接蛋白（Cx）组成，在大多数身体组织的细胞间通讯中发挥着重要作用。本文重点介绍了存在于骨骼组织中的 GJ 和 Cx。Cx43 是表达最丰富的连接蛋白，参与形成细胞间通讯的 GJ 和与外部环境通讯的半通道（HC）。通过长的树突状细胞质过程中的 GJ，嵌入在深陷窝中的骨细胞不仅能够与相邻的骨细胞，而且能够与位于骨表面的骨细胞形成功能性合胞体，尽管周围有矿化基质。功能性合胞体允许通过钙波、营养物质和合成代谢和/或分解代谢因子的广泛传播来协调细胞活动。作为机械感受器，骨细胞能够将机械刺激转化为生物信号，通过合胞体传播以协调骨重塑。大量研究证实了 Cx 和 GJ 的基本作用，这些研究强调了 Cx 和 GJ 的上调和下调如何对骨骼发育和软骨功能产生关键影响。更好地了解生理和病理条件下的 GJ 和 Cx 机制可能有助于开发针对人类骨骼系统疾病治疗的治疗方法。
