title: Elevated marrow inflammatory cells and osteoclasts in subchondral osteosclerosis in human knee osteoarthritis.
abstract: Subchondral osteosclerosis, characterized by an increase of hypomineralized bone material, is a pathological hallmark of osteoarthritis. The cellular components in the subchondral marrow compartment that participate in this aberrant bone remodeling process remain to be elucidated. This study assessed the presence of marrow inflammatory cells and their relative abundance between nonsclerotic and sclerotic tissues in knee osteoarthritis. Bone samples from osteoarthritic knee tibial plateaus were stratified for histological analyses using computed tomography osteoabsorptiometry. Immunohistological analysis revealed the presence of CD20 (B-lymphocyte) and CD68 (macrophage), but not CD3 (T-lymphocyte) immunoreactive mononuclear cells in subchondral marrow tissues and their relative abundance was significantly increased in sclerotic compared with nonsclerotic bone samples. Multinucleated osteoclasts that stained positive for CD68 and tartrate-resistant acid phosphatase, predominantly associated with CD34-positive blood vessels and their abundance was strongly increased in sclerotic samples. Bone-specific alkaline phosphatase activity in outgrowth osteoblasts was induced by conditioned medium from nonsclerotic, but not sclerotic, bone pieces. These results suggest that an interaction between bone-resident cells and marrow inflammatory cells might play a role in aberrant bone remodeling leading to subchondral osteosclerosis. Elevated osteoclast activity in sclerotic bone suggests that bone formation and resorption activities are increased, yet uncoupled, in human knee osteoarthritis.
authors.affiliation: Osteoarthritis Research Center Basel, Orthopaedic Department, University Hospital Basel, Spitalstrasse 21, 4031 Basel, Switzerland.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Geurts
authors.affiliation: Institute of Anatomy, University of Basel, Pestalozzistrasse 20, 4056 Basel, Switzerland.
authors.forename: Amit
authors.initials: A
authors.lastname: Patel
authors.affiliation: Department of Orthopaedic Surgery and Traumatology, Kantonsspital Baselland-Bruderholz, 4104 Bruderholz, Switzerland.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Hirschmann
authors.affiliation: Osteoarthritis Research Center Basel, Orthopaedic Department, University Hospital Basel, Spitalstrasse 21, 4031 Basel, Switzerland.
authors.forename: Geert I
authors.initials: GI
authors.lastname: Pagenstert
authors.affiliation: Institute of Anatomy, University of Basel, Pestalozzistrasse 20, 4056 Basel, Switzerland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Müller-Gerbl
authors.affiliation: Osteoarthritis Research Center Basel, Orthopaedic Department, University Hospital Basel, Spitalstrasse 21, 4031 Basel, Switzerland.
authors.forename: Victor
authors.initials: V
authors.lastname: Valderrabano
authors.affiliation: Osteoarthritis Research Center Basel, Orthopaedic Department, University Hospital Basel, Spitalstrasse 21, 4031 Basel, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hügle
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology*; D017077:Culture Media, Conditioned; D005260:Female; D006801:Humans; D008297:Male; D020370:Osteoarthritis, Knee / Q000150:complications / Q000473:pathology*; D010006:Osteoblasts / Q000201:enzymology; D010010:Osteoclasts; D010026:Osteosclerosis / Q000276:immunology / Q000473:pathology*; D012189:Retrospective Studies
chemical_list: D017077:Culture Media, Conditioned
keywords: macrophages; osteoarthritis; osteoclast; osteosclerosis; subchondral bone