title: Calcitonin induces collagen synthesis and osteoblastic differentiation in human periodontal ligament fibroblasts.
abstract: BACKGROUND
  Extracellular matrix (ECM) secretion and osteogenic differentiation in periodontal ligament fibroblasts (PDLF) facilitate the neogenesis of alveolar bone, which is the cellular basis for alveolar bone repair. Calcitonin (CT) has been reported to play an important role in promoting ECM expression and inducing osteogenic differentiation in osteoblast, but its effects on PDLFs remain obscure.
  
  
  METHODS
  The expression of CT, transforming growth factor-beta 1(TGF-β1) and bone morphogenetic protein (BMP) in gingival crevicular fluid (GCF) was measured by ELISA. The effects of CT on collagen synthesis and osteogenic differentiation in hPDLFs were investigated by using the primarily cultured hPDLFs infected with adenovirus carrying the CT gene. Gene expression was measured by quantitative PCR and western blot.
  
  
  RESULTS
  The expression of CT in gingival crevicular fluid (GCF) of patients with periodontitis was significantly higher than that of healthy subjects. In addition, CT expression correlated with the clinical indexes including probing pocket depth (PPD), clinical attachment level (CAL), and gingival index (GI). The in vitro study demonstrated that overexpression of CT by adenovirus infection increased the expression of TGF-β1, collagen type I and III, and osteoblastic markers including BMP-2/-4, alkaline phosphatase and osteocalcin in human PDLFs. Moreover, CT-enhanced collagen synthesis was abrogated in hPDLFs transfected with TGF-β1 siRNA, and CT-induced osteoblastic differentiation was blocked in hPDLFs by BMPs inhibitor noggin.
  
  
  CONCLUSIONS
  These results suggest that CT promotes collagen synthesis and osteogenic differentiation in hPDLFs via the TGF-β1 and BMPs signaling pathways, respectively.
authors.affiliation: Department of Stomatology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yibo
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Stomatology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ye
authors.affiliation: Department of Stomatology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Department of Stomatology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Tian
authors.affiliation: Department of Stomatology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Department of Stomatology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Haocheng
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Stomatology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China. Electronic address: wang_dento@163.com.
authors.forename: Dalin
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Stomatology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China. Electronic address: caozhizh2014@163.com.
authors.forename: Zhizhong
authors.initials: Z
authors.lastname: Cao
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000469:Alkaline Phosphatase / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D055419:Bone Morphogenetic Protein 7 / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002116:Calcitonin / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects*; D002681:China; D003094:Collagen / Q000096:biosynthesis* / Q000187:drug effects*; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D018450:Disease Progression; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression; D005883:Gingival Crevicular Fluid / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010006:Osteoblasts / Q000187:drug effects; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D017622:Periodontal Attachment Loss; D010512:Periodontal Index; D010513:Periodontal Ligament / Q000187:drug effects* / Q000378:metabolism; D010514:Periodontal Pocket; D010518:Periodontitis / Q000378:metabolism; D011994:Recombinant Proteins; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C525718:BMP2 protein, human; C525809:BMP4 protein, human; C525819:BMP7 protein, human; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D024042:Collagen Type I; D024061:Collagen Type III; D011994:Recombinant Proteins; D053773:Transforming Growth Factor beta1; D015675:Osteocalcin; D002116:Calcitonin; D003094:Collagen; D000469:Alkaline Phosphatase
keywords: Calcitonin; ECM expression; Osteoblastic differentiation; Periodontitis