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

活化素是一种多功能蛋白质，属于转化生长因子B超家族，在骨形成的调控中起重要作用。激活素通过激活素I型和IL型丝氨酸/苏氨酸激酶受体发挥其细胞效应。卵泡抑素是一种激活素结合蛋白，可抑制激活素的生物学效应。在这项研究中，激活素A，卵泡抑素和激活素受体的免疫组化表达进行了研究，在大鼠骨折愈合过程中。激活素A在骨折端附近的骨膜中早期检测到微弱的激活素A，但在发生软骨内骨化的骨折间隙周围的软骨细胞中不存在。卵泡抑素抗体染色骨折端附近骨膜中的成骨细胞;在软骨内骨化部位的增殖、成熟和肥大的软骨细胞中观察到中度和强烈的染色。激活素A和卵泡抑素水平高，靠近新形成的骨小梁表面上的成骨细胞。此外，在多核破骨细胞样细胞存在的地方，还发现了激活素A的强烈定位。这项研究表明，激活素-卵泡抑素系统可能有助于骨折愈合过程中与骨形成和重塑相关的细胞事件。激活素I型和IL型受体在膜内和软骨内骨化部位共表达。在软骨内骨化中不存在激活素A的情况下激活素I型、II型和IIB型受体的表达表明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.