title: Clopidogrel Enhances Mesenchymal Stem Cell Proliferation Following Periodontitis.
abstract: Bone formation is dependent on the differentiation of osteoblasts from mesenchymal stem cells (MSCs). In addition to serving as progenitors, MSCs reduce inflammation and produce factors that stimulate tissue formation. Upon injury, MSCs migrate to the periodontium, where they contribute to regeneration. We examined the effect of clopidogrel and aspirin on MSCs following induction of periodontitis in rats by placement of ligatures. We showed that after the removal of ligatures, which induces resolution of periodontal inflammation, clopidogrel had a significant effect on reducing the inflammatory infiltrate. It also increased the number of osteoblasts and MSCs. Mechanistically, the latter was linked to increased proliferation of MSCs in vivo and in vitro. When given prior to inducing periodontitis, clopidogrel had little effect on MSC or osteoblasts numbers. Applying aspirin before or after induction of periodontitis did not have a significant effect on the parameters measured. These results suggest that clopidogrel may have a positive effect on MSCs in conditions where a reparative process has been initiated.
authors.affiliation: Department of Physiology and Pathology, Faculdade de Odontologia de Araraquara, UNESP-Univ Estadual Paulista-Araraquara, São Paulo, Brazil.
authors.forename: L S
authors.initials: LS
authors.lastname: Coimbra
authors.affiliation: Department of Physiology and Pathology, Faculdade de Odontologia de Araraquara, UNESP-Univ Estadual Paulista-Araraquara, São Paulo, Brazil.
authors.forename: J P
authors.initials: JP
authors.lastname: Steffens
authors.affiliation: Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Alsadun
authors.affiliation: Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Albiero
authors.affiliation: Department of Diagnosis and Surgery, Faculdade de Odontologia de Araraquara, UNESP-Univ Estadual Paulista-Araraquara, São Paulo, Brazil.
authors.forename: C
authors.initials: C
authors.lastname: Rossa
authors.affiliation: Department of Medicine and Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Pignolo
authors.affiliation: Department of Physiology and Pathology, Faculdade de Odontologia de Araraquara, UNESP-Univ Estadual Paulista-Araraquara, São Paulo, Brazil.
authors.forename: L C
authors.initials: LC
authors.lastname: Spolidorio
authors.affiliation: Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA dtgraves@dental.upenn.edu.
authors.forename: D T
authors.initials: DT
authors.lastname: Graves
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects*; D000077144:Clopidogrel; D005881:Gingiva / Q000166:cytology / Q000473:pathology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000502:physiology; D010006:Osteoblasts / Q000187:drug effects / Q000502:physiology; D010518:Periodontitis / Q000473:pathology / Q000503:physiopathology*; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D058921:Purinergic P2Y Receptor Antagonists; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin
keywords: aspirin; gingiva; inflammation; osteoblast; periodontal diseases; regeneration