title: Plasminogen activator inhibitor-1 is involved in impaired bone repair associated with diabetes in female mice.
abstract: Previous studies suggest that fracture healing is impaired in diabetes; however, the underlying mechanism remains unclear. Here, we investigated the roles of plasminogen activator inhibitor-1 (PAI-1) in the impaired bone repair process by using streptozotocin (STZ)-induced diabetic female wild-type (PAI-1+/+) and PAI-1-deficient (PAI-1-/-) mice. Bone repair and the number of alkaline phosphatase (ALP)-positive cells at the site of a femoral bone damage were comparable in PAI-1+/+ and PAI-1-/- mice without STZ treatment. Although the bone repair process was delayed by STZ treatment in PAI-1+/+ mice, this delayed bone repair was blunted in PAI-1-/- mice. The reduction in the number of ALP-positive cells at the site of bone damage induced by STZ treatment was attenuated in PAI-1-/- mice compared to PAI-1+/+ mice. On the other hand, PAI-1 deficiency increased the levels of ALP and type I collagen mRNA in female mice with or without STZ treatment, and the levels of Osterix and osteocalcin mRNA, suppressed by diabetic state in PAI-1+/+ mice, were partially protected in PAI-1-/- mice. PAI-1 deficiency did not affect formation of the cartilage matrix and the levels of types II and X collagen and aggrecan mRNA suppressed by STZ treatment, although PAI-1 deficiency increased the expression of chondrogenic markers in mice without STZ treatment. The present study indicates that PAI-1 is involved in the impaired bone repair process induced by the diabetic state in part through a decrease in the number of ALP-positive cells.
authors.affiliation: Department of Physiology and Regenerative Medicine, Kinki University Faculty of Medicine, Osaka, Japan.
authors.forename: Li
authors.initials: L
authors.lastname: Mao
authors.affiliation: Department of Physiology and Regenerative Medicine, Kinki University Faculty of Medicine, Osaka, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kawao
authors.affiliation: Department of Physiology and Regenerative Medicine, Kinki University Faculty of Medicine, Osaka, Japan.
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Tamura
authors.affiliation: Life Science Research Institute, Kinki University, Osaka, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Okumoto
authors.affiliation: Department of Physiology and Regenerative Medicine, Kinki University Faculty of Medicine, Osaka, Japan.
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Okada
authors.affiliation: Department of Physiology and Regenerative Medicine, Kinki University Faculty of Medicine, Osaka, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Yano
authors.affiliation: Department of Physiology and Regenerative Medicine, Kinki University Faculty of Medicine, Osaka, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsuo
authors.affiliation: Department of Physiology and Regenerative Medicine, Kinki University Faculty of Medicine, Osaka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kaji
mesh_terms: D050156:Adipogenesis; D000818:Animals; D015415:Biomarkers; D001786:Blood Glucose; D001835:Body Weight; D001862:Bone Resorption / Q000235:genetics; D001842:Bone and Bones / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D020219:Chondrogenesis / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005269:Femur / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D051379:Mice; D018345:Mice, Knockout; D010010:Osteoclasts / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology*
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D017395:Plasminogen Activator Inhibitor 1