Marsell Richard, Jonsson Kenneth B, Cho Tae-Joon, Einhorn Thomas A, Ohlsson Claes, Schipani Ernestina
Department of Surgical Sciences, Uppsala University Hospital, Sweden.
Acta Orthop. 2007 Feb;78(1):39-45. doi: 10.1080/17453670610013402.
The parathyroid hormone-/parathyroid hormone-related protein (PTH/PTHrP) receptor plays a crucial role in endochondral bone formation and possibly also in fracture healing. Patients with Jansen's metaphysial chondrodysplasia (JMC) have a gain-of-function mutation in the PTH/PTHrP receptor. Transgenic mice expressing JMC PTH/PTHrP receptor mutants in osteoblasts are characterized by increased trabecular bone formation and reduced osteoblastic activity at periosteal sites. We have analyzed the bone phenotype and studied the fracture healing process in this model.
We performed bone density analysis of tibiae from 17-week-old transgenic mice and controls. Also, tibial fractures were produced in 14-week-old mice. Fracture healing was examined by radiographic and histological analysis.
Transgenic mice had a lower total bone mineral content (BMC), by a factor of one-third. The changes were bone compartment-specific with an increase in trabecular bone volume and a decrease in cortical thickness. The calluses in the transgenic mice were smaller, with a reduction in BMC and mean cross-sectional area by a factor of one-half. Despite the smaller size, however, the morphology and progression through the healing process were similar in both transgenic and wild-type littermates.
We conclude that the constitutively active PTH/PTHrP receptor has compartment-specific effects on bone formation when expressed in osteoblasts. During fracture healing, however, both the periosteal and the endochondral processes are activated, leading to fracture healing that is temporally and morphologically normal, although the callus tissue is less prominent.
甲状旁腺激素/甲状旁腺激素相关蛋白（PTH/PTHrP）受体在软骨内骨形成中起关键作用，可能在骨折愈合中也发挥作用。患有詹森干骺端软骨发育不良（JMC）的患者，其PTH/PTHrP受体存在功能获得性突变。在成骨细胞中表达JMC PTH/PTHrP受体突变体的转基因小鼠，其特征为小梁骨形成增加，骨膜部位的成骨细胞活性降低。我们分析了该模型中的骨表型并研究了骨折愈合过程。
我们对17周龄转基因小鼠和对照小鼠的胫骨进行了骨密度分析。此外，对14周龄小鼠造成胫骨骨折。通过放射学和组织学分析检查骨折愈合情况。
转基因小鼠的总骨矿物质含量（BMC）降低了三分之一。这些变化具有骨区域特异性，小梁骨体积增加，皮质厚度减小。转基因小鼠的骨痂较小，BMC和平均横截面积减少了一半。然而，尽管骨痂尺寸较小，但转基因小鼠和野生型同窝小鼠在愈合过程中的形态和进展相似。
我们得出结论，组成型激活的PTH/PTHrP受体在成骨细胞中表达时，对骨形成具有区域特异性影响。然而，在骨折愈合过程中，骨膜和软骨内过程均被激活，导致骨折愈合在时间和形态上正常，尽管骨痂组织不那么明显。
