title: Human osteoblasts produce cathepsin K.
abstract: Healthy bone is a rigid yet living tissue that undergoes continuous remodeling. Osteoclasts resorb bone in the remodeling cycle. They secrete H(+)-ions and proteinases to dissolve bone mineral and degrade organic bone matrix, respectively. One of the main collagenolytic proteinase in osteoclasts is cathepsin K, a member of papain family cysteine proteinases. Recently, it has been shown that osteoblasts may contribute to organic matrix remodeling. We therefore investigated their ability to produce cathepsin K for this action. Trabecular bone samples were collected from patients operated due to a fracture of the femoral neck. Part of the bone was decalcified and the rest was used for cell isolation. Sections from the decalcified bone were immunostained with antibodies against cathepsin K. Isolated cells were characterized for their ability to form mineralized matrix and subsequently analyzed for their cathepsin K production by Western blotting and quantitative RT-PCR. Osteoblasts, bone lining cells and some osteocytes in situ showed cathepsin K immunoreactivity and osteoblast-like cells in vitro produced cathepsin K mRNA and released both 42 kDa pro- and 27 kDa processed cathepsin K to culture media. Osteoblastic cathepsin K may thus contribute to collagenous matrix maintenance and recycling of improperly processed collagen I. Whether osteoblastic cathepsin K synthesis has consequences in diseases characterized by abnormal bone matrix turnover remains to be investigated.
authors.affiliation: Institute of Biomedicine/Anatomy, Biomedicum Helsinki, PO Box 63, FI-00014 University of Helsinki, Finland. jami.mandelin@helsinki.fi
authors.forename: Jami
authors.initials: J
authors.lastname: Mandelin
authors.forename: Mika
authors.initials: M
authors.lastname: Hukkanen
authors.forename: Tian-Fang
authors.initials: TF
authors.lastname: Li
authors.forename: Matti
authors.initials: M
authors.lastname: Korhonen
authors.forename: Mikko
authors.initials: M
authors.lastname: Liljeström
authors.forename: Tarvo
authors.initials: T
authors.lastname: Sillat
authors.forename: Roeland
authors.initials: R
authors.lastname: Hanemaaijer
authors.forename: Jari
authors.initials: J
authors.lastname: Salo
authors.forename: Seppo
authors.initials: S
authors.lastname: Santavirta
authors.forename: Yrjö T
authors.initials: YT
authors.lastname: Konttinen
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D002113:Calcification, Physiologic; D056657:Cathepsin K; D002403:Cathepsins / Q000096:biosynthesis* / Q000235:genetics; D002454:Cell Differentiation; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D053509:Matrix Metalloproteinase 13 / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D053244:Osteoprotegerin / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; C493709:RUNX2 protein, human; C505688:TNFSF11 protein, human; D014409:Tumor Necrosis Factor-alpha; D000469:Alkaline Phosphatase; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K; D053509:Matrix Metalloproteinase 13