title: Acid attack and cathepsin K in bone resorption around total hip replacement prosthesis.
abstract: Normal bone remodeling and pathological bone destruction have been considered to be osteoclast-driven. Osteoclasts are able to attach to bare bone surface and produce an acidic subcellular space. This leads to acid dissolution of hydroxyapatite, allowing cathepsin K to degrade the organic type I collagen-rich osteoid matrix under the acidic condition prevailing in Howship lacunae. Using a sting pH electrode, the interface membrane around a loosened total hip replacement prosthesis was found to be acidic. Confocal laser scanning disclosed irregular demineralization of the bone surface in contact with the acidic interface. Cathepsin K, an acidic collagenolytic enzyme, was found in interface tissue macrophages/giant cells and pseudosynovial fluid. Tissue extracts contained high levels of cathepsin K messenger RNA (mRNA) and protein. These observations suggest the presence of an acid- and cathepsin K-driven pathological mechanism of bone resorption, mediated not by osteoclasts in subosteoclastic space, but rather by the uncontrolled activity of macrophages in extracellular space.
authors.affiliation: Institute of Biomedicine, Department of Anatomy, University of Helsinki, Finland.
authors.forename: Y T
authors.initials: YT
authors.lastname: Konttinen
authors.forename: M
authors.initials: M
authors.lastname: Takagi
authors.forename: J
authors.initials: J
authors.lastname: Mandelin
authors.forename: J
authors.initials: J
authors.lastname: Lassus
authors.forename: J
authors.initials: J
authors.lastname: Salo
authors.forename: M
authors.initials: M
authors.lastname: Ainola
authors.forename: T F
authors.initials: TF
authors.lastname: Li
authors.forename: I
authors.initials: I
authors.lastname: Virtanen
authors.forename: M
authors.initials: M
authors.lastname: Liljestrom
authors.forename: H
authors.initials: H
authors.lastname: Sakai
authors.forename: Y
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: T
authors.initials: T
authors.lastname: Sorsa
authors.forename: R
authors.initials: R
authors.lastname: Lappalainen
authors.forename: A
authors.initials: A
authors.lastname: Demulder
authors.forename: S
authors.initials: S
authors.lastname: Santavirta
mesh_terms: D000143:Acids / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000378:metabolism; D019644:Arthroplasty, Replacement, Hip; D001862:Bone Resorption / Q000378:metabolism*; D056657:Cathepsin K; D002403:Cathepsins / Q000235:genetics / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019736:Prostheses and Implants; D011475:Prosthesis Failure
chemical_list: D000143:Acids; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C534130:CTSK protein, human; D056657:Cathepsin K