TY - JOUR
T1 - Teriparatide (human PTH1–34) compensates for impaired fracture healing in COX-2 deficient mice
AU - Yukata, Kiminori
AU - Xie, Chao
AU - Li, Tian Fang
AU - Brown, Matthew L.
AU - Kanchiku, Tsukasa
AU - Zhang, Xinping
AU - Awad, Hani A.
AU - Schwarz, Edward M.
AU - Beck, Christopher A.
AU - Jonason, Jennifer H.
AU - O'Keefe, Regis J.
N1 - Funding Information:
We are grateful Mike Thullen, Ryan Tierny, Sarah Mack, Abbie Turner and Donna Hoak for their assistance with microCT, histology and animal care. This study is supported by grants from the NIH (R01 AR048681v, P50 AR054041, and P30 AR061307).
Publisher Copyright:
© 2018
PY - 2018/5
Y1 - 2018/5
N2 - Genetic ablation of cyclooxygenase-2 (COX-2) in mice is known to impair fracture healing. To determine if teriparatide (human PTH1–34) 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 PTH1–34 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. PTH1–34 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 PTH1–34 for callus remodeling, TRAP staining was performed. Intermittent PTH1–34 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 PTH1–34 treatment could compensate for COX-2 deficiency and improve impaired fracture healing in Cox-2-deficient mice.
AB - Genetic ablation of cyclooxygenase-2 (COX-2) in mice is known to impair fracture healing. To determine if teriparatide (human PTH1–34) 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 PTH1–34 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. PTH1–34 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 PTH1–34 for callus remodeling, TRAP staining was performed. Intermittent PTH1–34 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 PTH1–34 treatment could compensate for COX-2 deficiency and improve impaired fracture healing in Cox-2-deficient mice.
KW - Cyclooxygenase-2 (COX-2)
KW - Fracture healing
KW - Parathyroid hormone (PTH)
KW - Periosteum
KW - Prostaglandin
UR - http://www.scopus.com/inward/record.url?scp=85041541405&partnerID=8YFLogxK
U2 - 10.1016/j.bone.2018.02.001
DO - 10.1016/j.bone.2018.02.001
M3 - Article
C2 - 29408411
AN - SCOPUS:85041541405
VL - 110
SP - 150
EP - 159
JO - Bone
JF - Bone
SN - 8756-3282
ER -