title: Upregulation of ANK protein expression in joint tissue in calcium pyrophosphate dihydrate crystal deposition disease.
abstract: OBJECTIVE
  Accumulation of excess extracellular inorganic pyrophosphate leads to calcium pyrophosphate dihydrate (CPPD) crystal formation in articular cartilage. CPPD crystal formation occurs near morphologically abnormal chondrocytes resembling hypertrophic chondrocytes. The ANK protein was recently implicated as an important factor in the transport of intracellular inorganic pyrophosphate across the cell membrane. We characterized ANK in joint tissues from patients with and without CPPD deposition and correlated the presence of ANK with markers of chondrocyte hypertrophy.
  
  
  METHODS
  Articular tissues were obtained from 24 patients with CPPD crystal deposition disease, 11 patients with osteoarthritis (OA) without crystals, and 6 controls. We determined the number of ANK-positive cells in joint tissues using immunohistochemistry and in situ hybridization, and correlated ANK positivity with markers of chondrocyte hypertrophy including Runx2, type X collagen, osteopontin (OPN), and osteocalcin (OCN).
  
  
  RESULTS
  ANK was detected in synoviocytes, chondrocytes, osteoblasts, and osteocytes. ANK was seen extracellularly only in the matrix of cartilage and meniscus. The number of ANK-positive cells was significantly higher in CPPD than in OA or normal joint tissues. The amount and intensity of ANK immunoreactivity reached maximum levels in the large chondrocytes around crystal deposits. ANK was similarly distributed to and significantly correlated with Runx2, type X collagen, OPN, and OCN.
  
  
  CONCLUSIONS
  ANK levels were higher in articular tissues from patients with CPPD deposition. ANK was concentrated around crystal deposits and correlated with markers of chondrocyte hypertrophy. These findings support a role for ANK in CPPD crystal formation in cartilage.
authors.affiliation: From the Department of Pathology, Division of Leading Pathophysiology, Iwate Medical University, School of Medicine, Iwate, Japan; Division of Rheumatology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA; Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Miwa
authors.initials: M
authors.lastname: Uzuki
authors.forename: Takashi
authors.initials: T
authors.lastname: Sawai
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Ryan
authors.forename: Ann K
authors.initials: AK
authors.lastname: Rosenthal
authors.forename: Ikuko
authors.initials: I
authors.lastname: Masuda
mesh_terms: D000328:Adult; D000368:Aged; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D002805:Chondrocalcinosis / Q000378:metabolism* / Q000473:pathology; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007596:Joints / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D028061:Phosphate Transport Proteins / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C498770:ANKH protein, human; D028061:Phosphate Transport Proteins
keywords: ANK; CALCIUM PYROPHOSPHATE DIHYDRATE; CARTILAGE; IMMUNOHISTOCHEMISTRY; IN SITU HYBRIDIZATION; PATHOLOGY