Immunohistochemical Detection of Activin A,Follistatin, and Activin Receptors during Fracture Healing in the Rat

激活素是一种多功能蛋白，属于转化生长因子-B超家族，被认为在调节骨形成方面发挥着重要作用。激活素通过激活素-I和IL-丝氨酸/苏氨酸激酶受体发挥细胞效应。卵泡抑素是一种激活素结合蛋白，可以抑制阿替丁的生物效应。本研究对大鼠骨折愈合过程中激活素A、卵泡抑素和激活素受体的免疫组织化学表达进行了研究。早期，激活素A在骨折端附近的骨膜中表达较弱，而在骨折间隙周围的软骨细胞中未检测到激活素A，在那里发生了软骨内成骨。在骨折端附近的骨膜中，一种抗卵泡抑素染色的成骨细胞的抗体；在软骨内骨化部位，增殖的、成熟的和肥大的软骨细胞呈中等和强烈的染色。在新形成的松质骨表面，激活素A和卵泡抑素在成骨细胞附近水平较高。此外，激活素A在存在多核破骨细胞样细胞的地方有强烈的定位。这项研究表明激活素-卵泡抑素系统可能参与了与骨折愈合过程中骨的形成和重塑相关的细胞事件。激活素I和IL受体在膜内和软骨内骨化部位共表达。在软骨内骨化中，激活素I、II和IIB受体的表达不存在激活素A，提示激活素的其他亚型可能通过这些受体发出信号。

Activins are multifunctional proteins that belong to the transforming growth factor-B superfamily and are thought to play an important role in modulatin the formation of bone. Activins exert their cellular effects by way of activin type-I and type-IL serine/threonine kinase receptors. Follistatin is an activin-binding protein that can suppress the biological effects of aetivins. In this study, the immunohistochemical expression of activin A, follistatin, and activin receptors was studied during fracture healing in the rat. Activin A was weakly detected in the periosteum near the fracture ends at an early stage but was absent in the chondrocytes around the fracture gap, where endochondral ossification took place. An antibody to follistatin stained osteogenic cells in the periosteum near the fracture ends ; moderate and strong staining were observed in proliferating, mature, and hypertrophied chondrocytes at the sites of endochondral ossification. Levels of activin A and follistatin were high near the osteoblasts on the surface of the newly formed trabecular bone. In addition, an intense localization of activin A was noted where multinucleated ostcoclast-like cells were present. This study suggests that the activin-follistatin system may contribute to cellular events related to the formation and remodeling of bone during fracture healing. Activin type-I and type-IL receptors were co-expressed in intramembranous and endochondral ossification sites. The expression of activin type-I, type-II, and type-IIB receptors in the absence of activin A in the endochondral ossification suggests that other isoforms of activins may signal by way of these receptors.