Collin-Osdoby P, Nickols G A, Osdoby P
Department of Biology, Washington University, St. Louis, Missouri 63130, USA.
J Cell Biochem. 1995 Mar;57(3):399-408. doi: 10.1002/jcb.240570305.
A large array of factors serve as vital communication links between cells and the characterization, regulation, and mechanisms of action of such factors are topics of intense research efforts. Most intercellular messenger molecules which have been described over the years are represented by proteins, small peptides, amino acids or their derivatives, ions, lipid metabolites, or steroids. However, a small uncharged free radical, nitric oxide, has recently garnered much attention as a potent multifunctional signal molecule with widespread actions within and between diverse tissues. Biochemical, molecular, and regulatory studies of the family of enzymes responsible for nitric oxide synthesis, nitric oxide synthases, have established that there are at least three distinct isoforms of this enzyme which are differentially expressed and regulated in various cells or tissues. Modulation of these isoenzyme levels or activities by diverse signals is mediated via transcriptional, translational, and/or post-translational mechanisms, and consequently, alterations in such control may influence normal or pathological processes. Nitric oxide appears to exert pronounced effects on skeletal physiology and its production by various bone cells, elicited target cell responses, modulation by other signalling molecules (e.g., cytokines, hormones, fatty acid derivatives), and chemical interactions with other free radicals (e.g., superoxide anions, hydroxyl radicals) may form one important facet of the many complicated communication pathways controlling bone cell physiology and remodeling. Further cell and molecular studies are needed to address the precise roles that nitric oxide plays in bone development and in the formation and degradation of bone during ordinary bone metabolism. In addition, alterations in the regulation and action of the bone nitric oxide system as a function of certain bone disorders may be manifested by perturbations in bone integrity or mineral homeostasis. In this article, we review the current evidence implicating nitric oxide as an important messenger molecule in bone intercellular communication, speculate on potential roles for this radical in bone biology, and discuss possible future directions for advanced research into the function of nitric oxide in skeletal physiology.
大量因素充当细胞间至关重要的通讯纽带，此类因素的特性、调控及其作用机制是深入研究的课题。多年来已描述的大多数细胞间信使分子包括蛋白质、小肽、氨基酸或其衍生物、离子、脂质代谢产物或类固醇。然而，一种不带电荷的小自由基——一氧化氮，最近作为一种强大的多功能信号分子备受关注，它在不同组织内部及之间具有广泛作用。对负责一氧化氮合成的酶家族——一氧化氮合酶的生化、分子和调控研究已证实，该酶至少有三种不同的同工型，它们在各种细胞或组织中差异表达和调控。不同信号对这些同工酶水平或活性的调节通过转录、翻译和/或翻译后机制介导，因此，这种调控的改变可能影响正常或病理过程。一氧化氮似乎对骨骼生理有显著影响，各种骨细胞产生一氧化氮、引发靶细胞反应、受其他信号分子（如细胞因子、激素、脂肪酸衍生物）调节以及与其他自由基（如超氧阴离子、羟基自由基）发生化学相互作用，可能构成控制骨细胞生理和重塑的众多复杂通讯途径的一个重要方面。需要进一步开展细胞和分子研究，以明确一氧化氮在骨骼发育以及正常骨代谢过程中骨的形成和降解中所起的精确作用。此外，作为某些骨疾病的一种表现，骨一氧化氮系统的调控和作用改变可能体现为骨完整性或矿物质稳态的紊乱。在本文中，我们综述了当前表明一氧化氮是骨细胞间通讯中重要信使分子的证据，推测该自由基在骨生物学中的潜在作用，并讨论未来对一氧化氮在骨骼生理功能方面进行深入研究可能的方向。
