Abstract
Chondrocalcinosis is a metabolic disease caused by the presence of calcium pyrophosphate dihydrate crystals in the synovial fluid. The goal of our endeavor was to find out whether short peptides could be used as a dissolving factor for such crystals. In order to identify peptides able to dissolve crystals of calcium pyrophosphate, we screened through a random library of peptides using a phage display. The first screening was designed to select phages able to bind the acidic part of alendronic acid (pyrophosphate analog). The second was a catalytic assay in the presence of crystals. The best-performing peptides were subsequently chemically synthesized and rechecked for catalytic properties. One peptide, named R25, turned out to possess some hydrolytic activity toward crystals. Its catalysis is Mg2+-dependent and also works against soluble species of pyrophosphate.
Highlights
Calcium pyrophosphate deposition (CPPD) is a metabolic disease primarily affecting the elderly population, and it is characterized by the deposition of calcium pyrophosphate (CaPP) crystals in synovial fluid
Screening of random bacteriophage libraries against immobilized alendronic acid and subsequent catalytic selection led us to five peptides with potential hydrolytic properties toward CaPP crystals
Incubation of chemically synthesized peptides singled out one of them—R25—as able to lower the amount of pyrophosphate by approximately 20% in 8 days
Summary
Calcium pyrophosphate deposition (CPPD) is a metabolic disease primarily affecting the elderly population, and it is characterized by the deposition of calcium pyrophosphate (CaPP) crystals in synovial fluid. The presence of crystals may not result in symptoms, but be present as an incidental finding of chondrocalcinosis (CC) during X-ray imaging, or present as painless lumps. They can contribute to acute CaPP crystal arthritis or chronic arthropathy with structural changes in osteoarthritis [1,2]. In the UK, prevalence was approximately 10–15% in a community sample of 65–75 year-olds; and above 40% of the over-80 population suffer from CPPD associated symptoms [5,6,7] It had a prevalence of 0.42% in an Italian population survey, making it the fourth most common musculoskeletal condition [8]
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