Factors affecting the solubility of calcium pyrophosphate dihydrate crystals.

Area of Science:

• Biochemistry
• Crystal Chemistry
• Rheumatology

Background:

• Triclinic calcium pyrophosphate dihydrate (CPPD) crystal deposition disease is a common condition.
• Understanding CPPD crystal solubility is crucial for explaining its pathogenesis and inflammatory potential.

Purpose of the Study:

• To quantify the solubility of CPPD crystals under various physiological conditions.
• To identify factors influencing CPPD crystal dissolution and their implications for joint inflammation.

Main Methods:

• Utilized 45Ca-labeled CPPD crystals to measure solubility in micromoles per liter.
• Incubated crystals in Tris-HCl buffer at varying pH, ionic strength, and concentrations of Mg++, citrate, and albumin.
• Assessed the impact of ionized calcium levels and enzymatic hydrolysis of pyrophosphate.

Main Results:

• CPPD crystal solubility was 60µM in 0.1-M Tris-HCl buffer (pH 7.4) at 37°C, reaching maximal solubility after 8 hours.
• Solubility increased with reduced crystal size, lower pH, higher ionic strength, and presence of Mg++, citrate, and albumin.
• Decreased ionized calcium (<5 mg/100 ml) significantly enhanced solubility; albumin's effect was attributed to calcium binding.
• Synovial fluid's low diffusible calcium (40% of total) suggests it's near the critical solubility-enhancing concentration.

Conclusions:

• Ionized calcium levels, pH, and specific ions/molecules significantly influence CPPD crystal solubility.
• Low ionized calcium in synovial fluid may promote CPPD crystal dissolution.
• Dissolution-induced crystal shedding could trigger inflammatory responses in the joint, potentially exacerbated by a fall in joint fluid pH.