title: PTH promotes allograft integration in a calvarial bone defect.
abstract: Allografts may be useful in craniofacial bone repair, although they often fail to integrate with the host bone. We hypothesized that intermittent administration of parathyroid hormone (PTH) would enhance mesenchymal stem cell recruitment and differentiation, resulting in allograft osseointegration in cranial membranous bones. Calvarial bone defects were created in transgenic mice, in which luciferase is expressed under the control of the osteocalcin promoter. The mice were given implants of allografts with or without daily PTH treatment. Bioluminescence imaging (BLI) was performed to monitor host osteprogenitor differentiation at the implantation site. Bone formation was evaluated with the aid of fluorescence imaging (FLI) and microcomputed tomography (μCT) as well as histological analyses. Reverse transcription polymerase chain reaction (RT-PCR) was performed to evaluate the expression of key osteogenic and angiogenic genes. Osteoprogenitor differentiation, as detected by BLI, in mice treated with an allograft implant and PTH was over 2-fold higher than those in mice treated with an allograft implant without PTH. FLI also demonstrated that the bone mineralization process in PTH-treated allografts was significantly higher than that in untreated allografts. The μCT scans revealed a significant increase in bone formation in allograft + PTH treated mice comparing to allograft + PBS treated mice. The osteogenic genes osteocalcin (Oc/Bglap) and integrin binding sialoprotein (Ibsp) were upregulated in the allograft + PTH treated animals. In summary, PTH treatment enhances osteoprogenitor differentiation and augments bone formation around structural allografts. The precise mechanism is not clear, but we show that infiltration pattern of mast cells, associated with the formation of fibrotic tissue, in the defect site is significantly affected by the PTH treatment.
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center , Los Angeles, California 90048, United States.
authors.forename: Dmitriy
authors.initials: D
authors.lastname: Sheyn
authors.forename: Doron
authors.initials: D
authors.lastname: Cohn Yakubovich
authors.forename: Ilan
authors.initials: I
authors.lastname: Kallai
authors.forename: Susan
authors.initials: S
authors.lastname: Su
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Da
authors.forename: Gadi
authors.initials: G
authors.lastname: Pelled
authors.forename: Wafa
authors.initials: W
authors.lastname: Tawackoli
authors.forename: Galen
authors.initials: G
authors.lastname: Cook-Weins
authors.forename: Edward M
authors.initials: EM
authors.lastname: Schwarz
authors.forename: Dan
authors.initials: D
authors.lastname: Gazit
authors.forename: Zulma
authors.initials: Z
authors.lastname: Gazit
mesh_terms: D064591:Allografts / Q000187:drug effects / Q000502:physiology; D000818:Animals; D016025:Bone Transplantation / Q000379:methods; D001842:Bone and Bones / Q000187:drug effects* / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D015675:Osteocalcin / Q000235:genetics; D010012:Osteogenesis / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012795:Sialoglycoproteins / Q000235:genetics; D014184:Transplantation, Homologous / Q000379:methods
chemical_list: D010281:Parathyroid Hormone; D012795:Sialoglycoproteins; D015675:Osteocalcin