GDFs promote tenogenic characteristics on human periodontal ligament-derived cells in culture at late passages.
Tendon/ligament injures are leading disabilities worldwide. The periodontal ligament (PDL) connects teeth to bone, and is comparable to a tendon/ligament-to-bone insertion. PDL-derived cells (PDLCs) express both osteo/cementogenesis and teno/ligamentogenesis genes. However, an efficient method to induce a tenogenic differentiation of PDLCs has not been thoroughly examined. Therefore, this study tested if growth/differentiation factors (GDFs) enhanced tenogenic characteristics of human PDLCs, as a potential cell source for tendon/ligament engineering. Results demonstrated recombinant GDF-5/GDF-7 inhibited alkaline phosphatase (ALP) activity of PDLCs from passage 3 to 6, while GDF-5 enhanced ALP in dental pulp-derived cells and mesenchymal stem cells. GDF-5 (particularly at 10 ng/ml concentration) induced high expression of both early (scleraxis) and mature (tenomodulin, aggrecan, collagen3) tenogenic genes in P4-6 PDLCs, while inhibiting expression of specific transcription-factors for osteogenic, chondrogenic and adipogenic differentiation. Exogenous GDFs might lead PDLCs being expanded in culture during several passages to highly useful cell source for tendon/ligament engineering.
Salivary Gland Disease Center and Molecular Laboratory for Gene Therapy & Tooth Regeneration, Capital Medical University School of Stomatology , Beijing , China .
Dengsheng
D
Xia
Yoshinori
Y
Sumita
Younan
Y
Liu
Yunlin
Y
Tai
Jinsong
J
Wang
Masataka
M
Uehara
Hideki
H
Agata
Hideaki
H
Kagami
Zhipeng
Z
Fan
Izumi
I
Asahina
Songlin
S
Wang
Simon D
SD
Tran
D000293:Adolescent; D000328:Adult; D053674:Aggrecans / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D003782:Dental Pulp / Q000166:cytology / Q000378:metabolism; D005260:Female; D055412:Growth Differentiation Factors / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D010513:Periodontal Ligament / Q000166:cytology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D053674:Aggrecans; D055412:Growth Differentiation Factors; D008565:Membrane Proteins; C422444:TNMD protein, human; D014157:Transcription Factors; D003094:Collagen