PLATELET-DERIVED GROWTH-FACTOR ENHANCES BONE CELL REPLICATION, BUT NOT DIFFERENTIATED FUNCTION OF OSTEOBLASTS
PLATELET-DERIVED GROWTH-FACTOR ENHANCES BONE CELL REPLICATION, BUT NOT DIFFERENTIATED FUNCTION OF OSTEOBLASTS
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DOI：
10.1210/en.134.3.1423
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发表时间：
1994-03-01
期刊：
影响因子：
4.8
通讯作者：
CANALIS, E
中科院分区：
文献类型：
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作者：
HOCK, JM;CANALIS, E
血小板衍生生长因子（PDGF）是一种多肽有丝分裂原，是由PDGF- aa和-BB链组成的二聚体。在大鼠中，PDGF-BB是普遍的循环形式，而在骨中，PDGF-AA是由未受刺激的正常骨细胞分泌的同种异构体。虽然PDGF-BB增加了胎鼠颅骨DNA合成，但对胶原合成的影响很小且不一致。为了定位对PDGF AA和BB亚型有反应的颅骨膜细胞，我们培养了21日龄胎鼠颅骨，以评估人重组PDGF-AA和-BB对骨细胞复制和基质形成的影响。使用组织形态学和放射自显影术评估变化，并使用生化分析与胶原合成和[H-3]胸腺嘧啶掺入的影响相关。PDGF-AA和- bb在0.03-3.3 nM （1-100 ng/ml）下作用24-72 h，使DNA合成增加1.5- 3倍；PDGF-BB比PDGF-AA更有效。尽管PDGF增加了所有细胞区的细胞复制，但PDGF-AA和-BB的作用在骨膜成纤维细胞区优先更大，其中，在3.3 nM时，AA的标记指数（LI）增加了3倍，BB的标记指数增加了5倍。AA和BB分别使骨表面细胞（成骨细胞）层的细胞复制增加了2倍和2.5倍，而AA和BB分别使中间成骨细胞区细胞复制增加了50%和2.5倍。细胞复制的增加与骨基质形成表面的显著抑制有关，在连续治疗24-72小时后，同等剂量的PDGF-BB比-AA更有效。连续或间歇暴露于PDGF- aa或PDGF- BB 24-72小时，既不刺激大鼠颅骨中胶原合成的速度，也不刺激有组织的骨基质形成。此外，0.03-3.3 nM的PDGF-BB可使破骨细胞数量和侵蚀表面百分比增加2- 3倍。我们的研究表明PDGF-AA和-BB是影响多种骨细胞的丝裂原，包括成骨细胞和破骨细胞谱系。PDGF严重破坏和抑制了骨基质的形成，没有证据表明在这些实验的时间框架内，含有[H-3]胸苷嘧啶的细胞分化为成熟的成骨细胞。在胎鼠颅骨中，PDGF治疗最显著的结果是选择性刺激成纤维细胞的复制和功能。
Platelet-derived growth factor (PDGF), a polypeptide mitogen, is a dimer composed of PDGF-AA and -BB chains. In rats, PDGF-BB is the prevalent circulating form, whereas in bone, PDGF-AA is the isoform secreted by unstimulated normal bone cells. Although PDGF-BB increased DNA synthesis in fetal rat calvariae, the effects on collagen synthesis were small and inconsistent. To localize the cells in the cranial periosteum that were responding to PDGF isoforms AA and BB, we cultured 21-day-old fetal rat calvariae to assess the effects of human recombinant PDGF-AA and -BB on bone cell replication and matrix formation. Changes were assessed using histomorphometry and autoradiography and correlated with effects on collagen synthesis and [H-3]thymidine incorporation, using biochemical assays.PDGF-AA and -BB at 0.03-3.3 nM (1-100 ng/ml) for 24-72 h increased DNA synthesis by 1.5- to 3-fold; PDGF-BB was more potent than PDGF-AA. Although PDGF increased cell replication in all cell zones, the effects of both PDGF-AA and -BB were preferentially greater in the periosteal fibroblast zone, in which, at 3.3 nM, the labeling index (LI) was increased by 3-fold with AA and by 5-fold with BB. Cell replication of the bone surface cell (osteoblast) layer was increased by 2-fold with AA and by 2.5-fold with BB, whereas replication in the intermediate osteoprogenitor zone increased by 50% with AA and by 2.5-fold with BB. The increase in cell replication was associated with a significant inhibition of bone matrix-forming surfaces, with PDGF-BB being more potent at equivalent doses than -AA after 24-72 h of continuous treatment. Continuous or intermittent exposure to PDGF-AA or PDGF BB for 24-72 h stimulated neither the rate of collagen synthesis nor organized bone matrix formation in rat calvariae. In addition, PDGF-BB at 0.03-3.3 nM increased the number of osteoclasts and the percent eroded surface by 2- to 3-fold. Our studies show that PDGF-AA and -BB are mitogens affecting multiple bone cells, including those of the osteoblast and osteoclast lineage. Treatment with PDGF severely disrupted and inhibited bone matrix formation, and there was no evidence to show that cells incorporating [H-3]thymidine differentiated into mature osteoblasts within the time frame of these experiments. In fetal rat calvaria, the most significant consequence of treatment with PDGF was the selective stimulation of fibroblast replication and function.