Hepatocyte growth factor and its actions in growth plate chondrocytes
Hepatocyte growth factor and its actions in growth plate chondrocytes
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DOI：
10.1016/8756-3282(96)00180-9
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发表时间：
1996-09-01
期刊：
影响因子：
4.1
通讯作者：
Roos, BA
中科院分区：
文献类型：
--
作者：
Grumbles, RM;Howell, DS;Roos, BA
肝细胞生长因子（HGF）是一种旁分泌调节因子，参与多种组织器官的发生和修复。本文研究了HGF在佝偻病大鼠生长板和增殖区软骨细胞中的表达和作用。体内和体外软骨细胞表达HGF mRNA; 1，25（OH）（2）具有三倍的最大刺激作用，其可被蛋白激酶C抑制剂H-7阻断。尽管HGF的产生和作用通常遵循旁分泌模型，但软骨细胞似乎能够表达和响应HGF，在生长软骨和衍生软骨细胞培养物中检测到编码HGF受体（c-met）的mRNA。在软骨细胞培养物中加入HGF可增加II型胶原mRNA和碱性磷酸酶活性，其程度与活性维生素D代谢产物相当。为了评估生物活性肽和HGF是否可以观察到类似的刺激作用，我们研究了HGF预处理对软骨细胞对合成人降钙素的急性反应的影响，人降钙素是一种合成代谢软骨细胞调节剂，其骨骼作用主要由cAMP升高和随后的蛋白激酶A活化介导，CT的蛋白激酶A的最大活化增加了由先前的HGF治疗从56%到78%，在音乐会上，我们的研究结果表明，除了在骨骼生长过程中HGF的经典旁分泌作用，这种生长因子可以调节激素的敏感性的软骨细胞在增殖，分化和/或凋亡。
Hepatocyte growth factor (HGF) has been implicated as a paracrine regulator of organogenesis and repair in many tissues, Here we have studied the expression and actions of HGF in intact rachitic rat growth plate and derived cultures of proliferative zone chondrocytes. In vivo and in vitro chondrocytes express HGF mRNA; 1,25(OH)(2) has a three-fold maximal stimulatory effect, which can be blocked by H-7, an inhibitor of protein kinase C, Although HGF elaboration and action generally follow a paracrine model, chondrocytes appear capable of both expressing and responding to HGF, mRNA encoding the HGF receptor (c-met) was detected in both growth cartilage and derived chondrocyte cultures. HGF addition to chondrocyte cultures increased collagen II mRNA and alkaline phosphatase enzymatic activity to degrees comparable to that observed for active vitamin D metabolites, Combining HGF and 1,25-D evoked a synergistic response (ninefold) of alkaline phosphatase activity, To assess whether a similar stimulatory effect might be seen with bioactive peptides and HGF, we investigated the effect of HGF pretreatment on acute responses of chondrocytes to synthetic human calcitonin, an anabolic chondrocyte regulator whose skeletal action are mediated principally by cAMP elevation and subsequent protein kinase A activation, CT's maximal activation of protein kinase A was increased by prior HGF treatment from 56% to 78%, In concert, our findings indicate that in addition to HGF's classical paracrine role during skeletal growth, this growth factor may modulate hormonal sensitivity of the chondrocyte during proliferation, differentiation, and/or apoptosis.