Parathyroid hormone regulates the expression of the receptor protein tyrosine phosphatase, OST-PTP, in rat osteoblast-like cells
Parathyroid hormone regulates the expression of the receptor protein tyrosine phosphatase, OST-PTP, in rat osteoblast-like cells
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DOI：
10.1210/en.137.3.925
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发表时间：
1996-03-01
期刊：
影响因子：
4.8
通讯作者：
Dixon, JE
中科院分区：
文献类型：
--
作者：
Mauro, LJ;Olmsted, EA;Dixon, JE
骨重建需要由特定的蛋白酪氨酸激酶（如c-src和c-fms）以及迄今为止未知的蛋白酪氨酸磷酸酶（PTP）介导的受调节的酪氨酸磷酸化。我们以前报道了一种新的骨特异性受体PTP的分离，命名为osteotestic PTP（OST-PTP），这是在成骨细胞分化和暴露于PTH后调节。为了确定这种PTH调节的相关性，我们将PTH诱导的UMR 106细胞中OST-PTP信使RNA（mRNA）的增加与PTH对相关受体PTP和PTH调节基因大鼠胶原酶的影响进行了比较。用大鼠PTH 1-34（rPTH）处理细胞导致OST-PTP mRNA的浓度和时间依赖性显著增加，阈值为4 h（小于或等于1 nM rPTH），最大反应为8 h（100 nM rPTH）时对照水平的6- 10倍。在100 pM rPTH下，胶原酶mRNA的增加可提前2小时检测到，最大反应至少是OST-PTP观察到的最大反应的5倍。结构相似的大鼠白细胞抗原相关分子PTP的mRNA水平不受rPTH处理的影响。放线菌酮（5-100 μ M）的管理废除了OST-PTP和胶原酶对PTH的反应。cAMP类似物CPT-cAMP（0.01-1 mM; 8 h）或Sp-cAMP（0.1和0.5 mM）在增强OST-PTP和胶原酶mRNA的有效性方面与rPTH相等或更大。相反，佛波醇酯、钙离子载体、牛PTH（3-34）或人PTRrP（7-34）对任一转录物均无影响。有趣的是，用表皮生长因子（10 ng/ml）（一种已知调节PTH作用的生长因子）预处理细胞36 h，导致rPTH暴露后OST-PTP mRNA丰度显著降低。这些研究表明，OST-PTP mRNA的调节是对PTH刺激的次级反应，其依赖于蛋白质合成，并且可能主要通过激活蛋白激酶A途径。骨受体PTP的这种特异性调节可能被证明是PTH调节成骨细胞功能的关键组成部分。
Bone remodeling requires regulated tyrosine phosphorylation mediated by specific protein tyrosine kinases, such as c-src and c-fms, and to date, unknown protein tyrosine phosphatases (PTPs). We previously reported the isolation of a novel bone-specific receptor PTP, named osteotesticular PTP (OST-PTP), which is regulated during osteoblast differentiation and after exposure to PTH. To determine the relevance of this PTH regulation, we characterized the PTH-induced increase in OST-PTP messenger RNA (mRNA) in UMR 106 cells in comparison with PTH effects on a related receptor PTP and a PTH regulated gene, rat collagenase. Treatment of cells with rat PTH 1-34 (rPTH) resulted in a dramatic concentration and time-dependent increase in OST-PTP mRNA with a threshold at 4 h (less than or equal to 1 nM rPTH) and maximal response of 6- 10-fold above control levels at 8 h (100 nM rPTH). An increase in collagenase mRNA was detectable 2 h earlier at 100 pM rPTH with a maximal response at least 5-fold greater than that observed for OST-PTP. Levels of mRNA for the structurally similar PTP, rat leucocyte antigen-related molecule, were unaffected by rPTH treatment. Administration of cycloheximide (5-100 mu M) abolished the OST-PTP and collagenase responses to PTH. The cAMP analogs, CPT-cAMP (0.01-1 mM; 8 h) or Sp-cAMP (0.1 and 0.5 mM) were equal or greater in their effectiveness to enhance both OST-PTP and collagenase mRNA as compared with rPTH. In contrast, phorbol esters, calcium ionophore, bovine PTH (3-34), or human PTRrP (7-34) had no effect on either transcript. Interestingly, 36 h of pretreatment of cells with epidermal growth factor (10 ng/ml), a growth factor known to modulate PTH's actions, resulted in a significant decrease in the abundance of OST-PTP mRNA after rPTH exposure. These studies suggest that regulation of OST-PTP mRNA is a secondary response to PTH stimulation that is dependent on protein synthesis and that may be primarily by activation of the protein kinase A pathway. This specific modulation of a bone receptor PTP may prove to be a critical component in the PTH modulation of osteoblast function.