Faculty Collaboration Database

Upregulation of ANK protein expression in joint tissue in calcium pyrophosphate dihydrate crystal deposition disease. J Rheumatol 2014 Jan;41(1):65-74

Date

12/03/2013

Pubmed ID

24293574

Pubmed Central ID

PMC6240442

DOI

10.3899/jrheum.111476

Scopus ID

2-s2.0-84891775364 (requires institutional sign-in at Scopus site)   14 Citations

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.

CONCLUSION: 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.

Author List

Uzuki M, Sawai T, Ryan LM, Rosenthal AK, Masuda I

Author

Ann K. Rosenthal MD Associate Dean, Chief, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Bone and Bones
Cartilage, Articular
Chondrocalcinosis
Chondrocytes
Female
Humans
Joints
Male
Middle Aged
Osteoarthritis
Phosphate Transport Proteins
Up-Regulation