Teriparatide (human PTH 1-34 ) compensates for impaired fracture healing in COX-2 deficient mice.

Autor: Yukata K; Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA; Department of Orthopedic Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan., Xie C; Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA., Li TF; Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA., Brown ML; Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA., Kanchiku T; Department of Orthopedic Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan., Zhang X; Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA., Awad HA; Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA., Schwarz EM; Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA., Beck CA; Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY, USA., Jonason JH; Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA., O'Keefe RJ; Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: okeefer@wudosis.wustl.edu.
Jazyk: angličtina
Zdroj: Bone [Bone] 2018 May; Vol. 110, pp. 150-159. Date of Electronic Publication: 2018 Feb 03.
DOI: 10.1016/j.bone.2018.02.001
Abstrakt: Genetic ablation of cyclooxygenase-2 (COX-2) in mice is known to impair fracture healing. To determine if teriparatide (human PTH 1-34 ) can promote healing of Cox-2-deficient fractures, we performed detailed in vivo analyses using a murine stabilized tibia fracture model. Periosteal progenitor cell proliferation as well as bony callus formation was markedly reduced in Cox-2 -/- mice at day 10 post-fracture. Remarkably, intermittent PTH 1-34 administration increased proliferation of periosteal progenitor cells, restored callus formation on day 7, and enhanced bone formation on days 10, 14 and 21 in Cox-2-deficient mice. PTH 1-34 also increased biomechanical torsional properties at days 10 or 14 in all genotypes, consistent with enhanced bony callus formation by radiologic examinations. To determine the effects of intermittent PTH 1-34 for callus remodeling, TRAP staining was performed. Intermittent PTH 1-34 treatment increased the number of TRAP positive cells per total callus area on day 21 in Cox-2 -/- fractures. Taken together, the present findings indicate that intermittent PTH 1-34 treatment could compensate for COX-2 deficiency and improve impaired fracture healing in Cox-2-deficient mice.
(Copyright © 2018 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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