title: Effects of cathepsin K on Emdogain-induced hard tissue formation by human periodontal ligament stem cells.
abstract: Recent studies have shown that patients with pycnodysostosis caused by cathepsin K (CTSK) genetic mutations exhibit significantly abnormal periodontal hard tissue structure. This finding suggests that CTSK may play a role in regulating the development of alveolar bone and cementum. However, the source of CTSK in the periodontal environment and the role of CTSK in periodontal regeneration, particularly hard tissue regeneration and development, remain unclear. After the isolation, cultivation, identification, and multi-lineage induction of human periodontal ligament stem cells (hPDLSCs), the present study used light and scanning electron microscopy, reverse-transcription quantitative polymerase chain reaction, western blotting, micro-computed tomography, immunohistochemical assays and ectopic hard tissue formation experiments to examine CTSK expression in hPDLSCs. The results indicated that CTSK expression was significantly upregulated in hPDLSCs during Emdogain induction but underwent minimal change during osteogenic or adipogenic induction. The present study also showed that the downregulation of CTSK expression inhibited osteogenic/cementogenic differentiation and ectopic hard tissue formation of hPDLSCs. It is therefore concluded that hPDLSCs expressed CTSK and that CTSK levels were significantly upregulated during Emdogain induction. Furthermore, CTSK promoted not only the osteogenic/cementogenic differentiation of hPDLSCs but also their ability to form ectopic hard tissue. These new findings may enhance the understanding of periodontal hard tissue development and functional regeneration. However, the specific underlying mechanisms require further investigation. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, China.|Shaanxi Key Laboratory of Stomatology, Biomaterials Unit, School of Stomatology, Fourth Military Medical University, Xi'an, China.|Department of Oral Medicine, Northwest Women's and Children's Hospital, Xi'an, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Paediatric Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: Zhi-Fei
authors.initials: ZF
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: An
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, China.|Shaanxi Key Laboratory of Stomatology, Biomaterials Unit, School of Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, China.|Shaanxi Key Laboratory of Stomatology, Biomaterials Unit, School of Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: Rui-Xin
authors.initials: RX
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, China.|Shaanxi Key Laboratory of Stomatology, Biomaterials Unit, School of Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yin
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral Biology, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China.|State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xue
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, China.|Shaanxi Key Laboratory of Stomatology, Biomaterials Unit, School of Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: Fa-Ming
authors.initials: FM
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D056657:Cathepsin K / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured; D002648:Child; D003746:Dental Enamel Proteins / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D016086:Lentivirus / Q000378:metabolism; D008297:Male; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects; D010513:Periodontal Ligament / Q000166:cytology*; D034741:RNA, Small Interfering / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*; D023822:Tissue Engineering; D055114:X-Ray Microtomography; D055815:Young Adult
chemical_list: D003746:Dental Enamel Proteins; D034741:RNA, Small Interfering; C109069:enamel matrix proteins; D056657:Cathepsin K
keywords: Emdogain; cathepsin K; cementum regeneration; functional periodontal regeneration; osteogenic regeneration; periodontal ligament stem cells (PDLSCs)