{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:03:32Z","timestamp":1791277412541,"version":"4.1.0"},"reference-count":68,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2002,12,12]],"date-time":"2002-12-12T00:00:00Z","timestamp":1039651200000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2002,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Excess accumulation of extracellular inorganic pyrophosphate (ePPi) in aged human cartilage is crucial in calcium pyrophosphate dihydrate (CPPD) crystal formation in cartilage matrix. Two sources of ePPi are ePPi\u2010generating ectoenzymes (NTPPPH) and extracellular transport of intracellular PPi by ANK. This study was undertaken to evaluate the role of NTPPPH and ANK in ePPi elaboration, by investigating expression of NTPPPH enzymes (cartilage intermediate\u2010layer protein [CILP] and plasma cell membrane glycoprotein 1 [PC\u20101]) and ANK in human chondrocytes from osteoarthritic (OA) articular cartilage containing CPPD crystals and without crystals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Chondrocytes were harvested from knee cartilage at the time of arthroplasty (OA with CPPD crystals [CPPD], n = 8; OA without crystals [OA], n = 10). Normal adult human chondrocytes (n = 1) were used as a control. Chondrocytes were cultured with transforming growth factor \u03b21 (TGF\u03b21), which stimulates ePPi elaboration, and\/or insulin\u2010like growth factor 1 (IGF\u20101), which inhibits ePPi elaboration. NTPPPH and ePPi were measured in the media at 48 hours. Media CILP, PC\u20101, and ANK were determined by dot\u2010immunoblot analysis. Chondrocyte messenger RNA (mRNA) was extracted for reverse transcriptase\u2013polymerase chain reaction to study expression of mRNA for CILP, PC\u20101, and ANK. NTPPPH and ANK mRNA and protein were also studied in fresh frozen cartilage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Basal ePPi elaboration and NTPPPH activity in conditioned media from CPPD chondrocytes were elevated compared with normal chondrocytes, and tended to be higher compared with OA chondrocytes. Basal expression of mRNA for CILP (chondrocytes) and ANK (cartilage) was higher in both CPPD chondrocytes and CPPD cartilage extract than in OA or normal samples. PC\u20101 mRNA was less abundant in CPPD chondrocytes and cartilage extract than in OA chondrocytes and extract, although the difference was not significant. CILP, PC\u20101, and ANK protein levels were similar in CPPD, OA, and normal chondrocytes or cartilage extracts. Both CILP and ANK mRNA expression and ePPi elaboration were stimulated by TGF\u03b21 and inhibited by IGF\u20101 in chondrocytes from all sources.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>CILP and ANK mRNA expression correlates with chondrocyte ePPi accumulation around CPPD and OA chondrocytes, and all respond similarly to growth factor stimulation. These findings suggest that up\u2010regulated CILP and ANK expression contributes to higher ePPi accumulation from CPPD crystal\u2013forming cartilage.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.10632","type":"journal-article","created":{"date-parts":[[2002,12,16]],"date-time":"2002-12-16T13:50:56Z","timestamp":1040046656000},"page":"3218-3229","source":"Crossref","is-referenced-by-count":74,"title":["Up\u2010regulated expression of cartilage intermediate\u2010layer protein and ANK in articular hyaline cartilage from patients with calcium pyrophosphate dihydrate crystal deposition disease"],"prefix":"10.1002","volume":"46","author":[{"given":"Jun","family":"Hirose","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence 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