Mice expressing a constitutively active PTH/PTHrP receptor in osteoblasts show reduced callus size but normal callus morphology during fracture healing

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Marsell, Richard; Jonsson, Kenneth B; Cho, Tae-Joon; Einhorn, Thomas A; Ohlsson, Claes; Schipani, Ernestina
Issue Date
Taylor & Francis
Acta Orthop 2007; 78(1): 39-45
Bone DensityBony Callus/anatomy & histology/metabolism/physiologyFracture Healing/genetics/*physiologyGene ExpressionMiceMice, TransgenicOsteoblasts/*metabolismOsteogenesis/genetics/physiologyReceptor, Parathyroid Hormone, Type 1/genetics/*metabolism/physiologyTibia/cytology/metabolism/pathologyTibial Fractures/metabolism/pathology/physiopathology
BACKGROUND: 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. METHODS: 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. RESULTS: 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. INTERPRETATION: 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.
1745-3674 (Print)
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College of Medicine/School of Medicine (의과대학/대학원)Orthopedic Surgery (정형외과학전공)Journal Papers (저널논문_정형외과학전공)
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