期刊
FRONTIERS IN BIOSCIENCE-LANDMARK
卷 10, 期 -, 页码 988-997出版社
FRONTIERS IN BIOSCIENCE INC
DOI: 10.2741/1593
关键词
inorganic pyrophosphate; pathology; calcification; articular cartilage; chondrocyte; review
资金
- NHLBI NIH HHS [HL077360] Funding Source: Medline
- NIAMS NIH HHS [AR049366] Funding Source: Medline
- NIA NIH HHS [P01AGO7996] Funding Source: Medline
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL077360] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R01AR049366] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [P01AG007996] Funding Source: NIH RePORTER
Physiologic levels of extracellular PPi, which suppresses hydroxyapatite crystal growth, must be maintained by articular chondrocytes and resident cells in many othee tissues in order to prevent pathologic calcification. However, extracellular PPi rises in articular cartilage in direct association with aging. Matrix supersaturation with PPi stimulates chondrocalcinosis manifesting as calcium pyrophosphate dihydrate (CPPD) crystal deposition. Extracellular PPi levels are normally held in check by balances in PPi generation by nucleotide pyrophosphatase phosphodiesterase (NPP/NTPPPH) activity relative to PPi degradation by pyrophosphatases, by balance effects of cytokines and growth factors, and by transport of PPi from the cell interior involving the multiple-pass transmembrane protein ANK. But these mechanisms become dysrgulated in aging and osteoarthritic (OA) cartilage and extracellular PPi excess supervenes, mediated in large part by upregulated NPP1 and ANK expression in articular cartilage. Conversely, NPP1 and ANK deficiency states were recently linked to phenotypically similar forms of spontaneous soft tissue calcification with hydroxyapatite ( HA). Here, we focus on recent advances in understanding of PPi metabolism and NPP1 and ANK function pertinent to the pathogenesis of pathologi matrix calcification in articular cartilage.
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