Lotinun Sutada, Sibonga Jean D, Turner Russell T
Department of Orthopedics, Mayo Clinic, Rochester, MN 55905, USA.
Endocrine. 2002 Feb;17(1):29-36. doi: 10.1385/ENDO:17:1:29.
A mechanism explaining the differential skeletal effects of intermittent and continuous elevation of serum parathyroid hormone (PTH) remains elusive. Intermittent PTH increases bone formation and bone mass and is being investigated as a therapy for osteoporosis. By contrast, chronic hyperparathyroidism results in the metabolic bone disease osteitis fibrosa characterized by osteomalacia, focal bone resorption, and peritrabecular bone marrow fibrosis. Intermittent and continuous PTH have similar effects on the number of osteoblasts and bone-forming activity. Many of the beneficial as well as detrimental effects of the hormone appear to be mediated by osteoblast-derived growth factors. This hypothesis was tested using cDNA microgene arrays to compare gene expression in tibia of rats treated with continuous and pulsatile administration of PTH. These treatments result in differential expression of many genes, including growth factors. One of the genes whose steady-state mRNA levels was increased by continuous but not pulsatile administration was platelet-derived growth factor-A (PDGF-A). Administration of a PDGF-A antagonist greatly reduced bone resorption, osteomalacia, and bone marrow fibrosis in a rat model for hyperparathyroidism, suggesting that PDGF-A is a causative agent for this disease. These findings suggest that profiling changes in gene expression can help identify the metabolic pathways responsible for the skeletal responses to the hormone.
间歇性和持续性血清甲状旁腺激素（PTH）升高对骨骼产生不同影响的机制仍不清楚。间歇性PTH可增加骨形成和骨量，目前正作为一种骨质疏松症治疗方法进行研究。相比之下，慢性甲状旁腺功能亢进会导致以骨软化、局灶性骨吸收和骨小梁周围骨髓纤维化为特征的代谢性骨病——纤维性骨炎。间歇性和持续性PTH对成骨细胞数量和骨形成活性有相似的影响。该激素的许多有益和有害作用似乎都是由成骨细胞衍生的生长因子介导的。使用cDNA微基因阵列比较连续和脉冲式给予PTH的大鼠胫骨中的基因表达，对这一假说进行了验证。这些处理导致许多基因的差异表达，包括生长因子。血小板衍生生长因子-A（PDGF-A）是连续而非脉冲式给药后其稳态mRNA水平升高的基因之一。在甲状旁腺功能亢进大鼠模型中，给予PDGF-A拮抗剂可大大减少骨吸收、骨软化和骨髓纤维化，这表明PDGF-A是该疾病的致病因子。这些发现表明，分析基因表达变化有助于确定导致骨骼对该激素产生反应的代谢途径。
