title: Co-expression of DKK-1 and Sclerostin in Subchondral Bone of the Proximal Femoral Heads from Osteoarthritic Hips.
abstract: Osteoarthritis (OA) is a progressively degenerative joint disease influenced by structural and metabolic factors. There is growing evidence that subchondral bone is involved in both symptomatic and structural progression in OA. The Wnt pathway has been implicated in the progression of OA but the expression and function of the Wnt inhibitors, Dikkopf (DKK-1) and sclerostin (SOST), are unclear.
  
  
  
  We examined the regional distribution of DKK-1 and SOST in subchondral bone of the femoral head using resection specimens following arthroplasty in patients presenting with end-stage OA. Cylindrical cores for immunohistochemistry were taken through midpoint of full thickness cartilage defect, partial cartilage defect, through base of osteophyte and through macroscopically normal cartilage.
  
  
  
  Subchondral bone was thickest in cores taken from regions with full cartilage defect and thinnest in cores taken from osteophyte regions. In subchondral bone, expression of both DKK-1 and SOST was observed exclusively in osteocytes. Expression was highest in subchondral bone in cores taken from regions with partial but not full thickness cartilage defects. DKK-1 but not SOST was expressed by chondrocytes in cores with macroscopically normal cartilage.
  
  
  
  The current study describes the regional cellular distribution of SOST and DKK-1 in hip OA. Expression was highest in the osteocytes in bone underlying partial thickness cartilage defects. It is however not clear if this is a cause or a consequence of alterations in the overlying cartilage. However, it is suggestive of an active remodeling process which might be targeted by disease-modifying agents.
authors.affiliation: Botnar Research Centre, Nuffield Department of Orthopaedics, NDORMS, Rheumatology and Musculoskeletal Sciences, University of Oxford, Old Road, Oxford, OX3 7LD, UK.
authors.forename: Allahdad
authors.initials: A
authors.lastname: Zarei
authors.affiliation: Botnar Research Centre, Nuffield Department of Orthopaedics, NDORMS, Rheumatology and Musculoskeletal Sciences, University of Oxford, Old Road, Oxford, OX3 7LD, UK.
authors.forename: Philippa A
authors.initials: PA
authors.lastname: Hulley
authors.affiliation: Botnar Research Centre, Nuffield Department of Orthopaedics, NDORMS, Rheumatology and Musculoskeletal Sciences, University of Oxford, Old Road, Oxford, OX3 7LD, UK.
authors.forename: Afsie
authors.initials: A
authors.lastname: Sabokbar
authors.affiliation: Botnar Research Centre, Nuffield Department of Orthopaedics, NDORMS, Rheumatology and Musculoskeletal Sciences, University of Oxford, Old Road, Oxford, OX3 7LD, UK. kassim.javaid@ndorms.ox.ac.uk.
authors.forename: M Kassim
authors.identifier: 0000-0001-7985-0048
authors.initials: MK
authors.lastname: Javaid
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D016723:Bone Remodeling / Q000502:physiology; D002358:Cartilage, Articular / Q000378:metabolism*; D019902:Chondrocytes / Q000378:metabolism; D005269:Femur / Q000378:metabolism*; D005819:Genetic Markers; D006615:Hip / Q000473:pathology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism*; D010011:Osteocytes / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; C501126:DKK1 protein, human; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; C422903:SOST protein, human
keywords: DKK-1; Osteoarthritis; SOST; Subchondral bone; Wnt