Department of Biological & Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
J Anat. 2010 Nov;217(5):574-87. doi: 10.1111/j.1469-7580.2010.01273.x.
A multitude of signalling cascades are implicated in the homeostasis of articular chondrocytes. However, the identity of these signalling pathways is not fully established. The 3, 5'-cyclic AMP-mediated signalling system is considered to be a prototype. Adenylyl cyclase (AC) is an effector enzyme responsible for the synthesis of cAMP. There are 10 mammalian AC isoforms and some of these are differentially regulated by calcium/calmodulin (Ca²(+) /CaM). Ca²(+) is known to play an important role in the development and maintenance of skeletal tissues. Ca²(+) /CaM-dependent AC isoforms and their temporal expression in articular chondrocytes in rats were identified using RT-PCR and immunohistochemistry techniques. All Ca²(+) /CaM-dependent AC isoforms were expressed in chondrocytes from all age groups examined. Each isoform was differentially expressed in developing and adult articular chondrocytes. Generally, expression of AC isoforms was observed to increase with age, but the increase was not uniform for all Ca²(+) /CaM-dependent AC isoforms. Expression of Ca²(+) /CaM-dependent AC isoforms along with other signalling molecules known to be present in articular chondrocytes indicate complicated and multifactorial signalling cascades involved in the development and homeostasis of articular cartilage. The significance of these findings in terms of articular chondrocyte physiology is discussed.
多种信号级联反应参与关节软骨细胞的动态平衡。然而,这些信号通路的身份尚未完全确定。3,5'-环腺苷酸介导的信号系统被认为是一个原型。腺苷酸环化酶(AC)是一种效应酶,负责合成 cAMP。哺乳动物中有 10 种 AC 同工型,其中一些受钙/钙调蛋白(Ca²(+) /CaM)的差异调节。Ca²(+) 在骨骼组织的发育和维持中起着重要作用。使用 RT-PCR 和免疫组织化学技术鉴定了大鼠关节软骨细胞中 Ca²(+) /CaM 依赖性 AC 同工型及其在其中的时空表达。所有 Ca²(+) /CaM 依赖性 AC 同工型均在所有检查年龄段的软骨细胞中表达。每种同工型在发育中和成年关节软骨细胞中的表达不同。通常,AC 同工型的表达随年龄的增长而增加,但并非所有 Ca²(+) /CaM 依赖性 AC 同工型的增加都是均匀的。Ca²(+) /CaM 依赖性 AC 同工型的表达以及其他已知存在于关节软骨细胞中的信号分子表明,参与关节软骨发育和动态平衡的信号级联反应复杂且多因素。讨论了这些发现对关节软骨细胞生理学的意义。