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.
复制标题
DOI：
10.1210/endo.134.3.8119182
复制
发表时间：
1994-03
期刊：
影响因子：
4.8
通讯作者：
Janet Hock;E. Canalis
中科院分区：
文献类型：
--
作者：
Janet Hock;E. Canalis
血小板衍生生长因子（PDGF）是一种多肽促分裂剂，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型。虽然PDGF-BB增加了胎鼠颅骨的DNA合成，但对胶原合成的影响很小且不一致。为了定位颅骨骨膜中对PDGF亚型AA和BB有反应的细胞，我们培养了21天龄的胎鼠颅骨，以评估人重组PDGF-AA和-BB对骨细胞复制和基质形成的影响。使用组织形态计量学和放射自显影术评估变化，并使用生物化学测定法将其与对胶原合成和[3 H]胸苷掺入的影响相关联。PDGF-AA和-BB在0.03-3.3 nM（1-100 ng/ml）下作用24-72 h可使DNA合成增加1.5- 3倍; PDGF-BB比PDGF-AA更有效。虽然PDGF在所有细胞区中增加细胞复制，但PDGF-AA和-BB两者的作用优先在骨膜成纤维细胞区中更大，其中，在3.3 nM下，标记指数（LI）用AA增加3倍，用BB增加5倍。骨表面细胞（成骨细胞）层的细胞复制增加了2倍，AA和BB的2.5倍，而在中间骨祖细胞区的复制增加了50%，AA和BB的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，PDGF-BB在等效剂量下比-AA更有效。连续或间歇性暴露于PDGF-AA或PDGF-BB 24-72小时既不刺激胶原合成的速率，也不刺激大鼠颅骨中有组织的骨基质形成。此外，0.03-3.3 nM的PDGF-BB使破骨细胞的数量和侵蚀表面的百分比增加2至3倍。我们的研究表明，PDGF-AA和-BB是影响多种骨细胞的有丝分裂原，包括成骨细胞和破骨细胞谱系。用PDGF处理严重破坏和抑制骨基质形成，并且没有证据表明掺入[3 H]胸苷的细胞在这些实验的时间范围内分化成成熟的成骨细胞。在胎鼠颅骨中，PDGF治疗的最显著结果是选择性刺激成纤维细胞复制和功能。
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 [3H]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 [3H]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.