title: Mice expressing a constitutively active PTH/PTHrP receptor in osteoblasts show reduced callus size but normal callus morphology during fracture healing.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Department of Surgical Sciences, Uppsala University Hospital, Sweden.
authors: Richard
authors: R
authors: Marsell
authors: Kenneth B
authors: KB
authors: Jonsson
authors: Tae-Joon
authors: TJ
authors: Cho
authors: Thomas A
authors: TA
authors: Einhorn
authors: Claes
authors: C
authors: Ohlsson
authors: Ernestina
authors: E
authors: Schipani
mesh_terms: D000818:Animals; D015519:Bone Density; D002146:Bony Callus / Q000033:anatomy & histology / Q000378:metabolism / Q000502:physiology; D017102:Fracture Healing / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000378:metabolism*; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D013977:Tibia / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D013978:Tibial Fractures / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
chemical_list: D044168:Receptor, Parathyroid Hormone, Type 1