title: Co-administration of aspirin and allogeneic adipose-derived stromal cells attenuates bone loss in ovariectomized rats through the anti-inflammatory and chemotactic abilities of aspirin.
abstract: BACKGROUND
  Osteoporosis is a syndrome of excessive skeletal fragility characterized by the loss of mass and deterioration of microarchitecture in bone. Single use of aspirin or adipose-derived stromal cells (ASCs) has been recognized recently to be effective against osteoporosis. The goal of the study was to evaluate the osteogenic effects of the co-administration of aspirin and allogeneic rat adipose-derived stromal cells (rASCs) on ovariectomized (OVX)-induced bone loss in rats. The underlying mechanisms were investigated in vitro and in vivo.
  
  
  METHODS
  Firstly, allogeneic rASCs were isolated and cultured, and the conditioned medium (CM) from the maintenance of rASCs was collected. Secondly, the OVX rats were administrated CM, rASCs, aspirin (ASP) or rASCs + ASP, respectively. Twelve weeks later, the anti-inflammatory and osteogenic effects were assessed by micro-CT, undecalcified histological sections, dynamic histomorphometric analyses and serologic assays for biochemical markers. Finally, a Transwell migration assay in vitro and cell-trafficking analyses in vivo were used to explore the effects of aspirin on rASC migration.
  
  
  RESULTS
  Systemic administration of aspirin and rASCs attenuated OVX-induced bone loss better than single use of aspirin or ASCs (p < 0.05, respectively). Next, we analyzed the underlying mechanisms of the anti-inflammatory and chemotactic abilities of aspirin. Aspirin suppressed serum levels of the pro-inflammatory cytokines on tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), and the anti-inflammatory ability was positively associated with bone morphometry. Also, aspirin exhibited excellent chemotactic effects in vitro and accelerated the homing of allogeneic rASCs into bone marrow during early in vivo stages.
  
  
  CONCLUSIONS
  Co-administered aspirin and allogeneic ASCs can partially reverse OVX-induced bone loss in rats. This effect appears to be mediated by the anti-inflammatory and chemotactic abilities of aspirin.
authors.affiliation: The Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, 100081, China. sdu2003@126.com.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: The Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, 100081, China. liwei3691@126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, China. kqliuyunsong@sohu.com.
authors.forename: Yunsong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, China. zx8213163@163.com.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, China. kqzhouysh@hsc.pku.edu.cn.|National Engineering Lab for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology, Beijing, 100081, China. kqzhouysh@hsc.pku.edu.cn.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D017667:Adipocytes / Q000166:cytology; D000818:Animals; D001241:Aspirin / Q000008:administration & dosage*; D001861:Bone Regeneration / Q000187:drug effects; D002118:Calcium / Q000097:blood; D002630:Chemotactic Factors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology; D010024:Osteoporosis / Q000097:blood / Q000188:drug therapy / Q000628:therapy*; D010052:Ovariectomy / Q000009:adverse effects; D051381:Rats; D011916:Rats, Inbred F344; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D002630:Chemotactic Factors; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D001241:Aspirin; D002118:Calcium