title: The role of protease-activated receptor-1 in bone healing.
abstract: Protease-activated receptor (PAR)-1, a G-protein-coupled receptor activated by thrombin, mediates thrombin-induced proliferation of osteoblasts. The current study was undertaken to define the role of PAR-1 in bone repair. Holes were drilled transversely through the diaphysis of both tibiae of PAR-1-null and wild-type mice. Three days later, fewer cells had invaded the drill site from adjacent bone marrow in PAR-1-null mice than in wild-type mice, and a lower percentage of cells were labeled with [(3)H]thymidine in PAR-1-null drill sites. More osteoclasts were also observed in the drill site of PAR-1-null mice than in wild-type mice 7 days after drilling. New mineralized bone area was less in the drill site and on the adjacent periosteal surface in PAR-1-null mice than in wild-type mice at day 9. From day 14, no obvious differences could be seen between PAR-1-null and wild-type tibiae. In vitro thrombin caused a dose-dependent increase in proliferation of bone marrow stromal cells isolated from wild-type mice but not PAR-1-null mice. Thrombin stimulated survival of bone marrow stromal cells from both wild-type and PAR-1-null mice, but it did not affect bone marrow stromal cell migration in either wild-type or PAR-1-null cells. The results indicate that PAR-1 plays an early role in bone repair.
authors.affiliation: School of Veterinary Science, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Shu Jun
authors.initials: SJ
authors.lastname: Song
authors.forename: Charles N
authors.initials: CN
authors.lastname: Pagel
authors.forename: Therese M
authors.initials: TM
authors.lastname: Campbell
authors.forename: Robert N
authors.initials: RN
authors.lastname: Pike
authors.forename: Eleanor J
authors.initials: EJ
authors.lastname: Mackie
mesh_terms: D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000166:cytology; D001861:Bone Regeneration; D001842:Bone and Bones / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D017931:DNA Primers / Q000737:chemistry; D005838:Genotype; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D044463:Receptor, PAR-1 / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000166:cytology; D013917:Thrombin / Q000378:metabolism; D013997:Time Factors
chemical_list: D017931:DNA Primers; D044463:Receptor, PAR-1; D012313:RNA; D011516:Prothrombin; D013917:Thrombin
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