Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease is characterized by deposits of triclinic (t) and monoclinic (m) CPPD crystals in articular and fibrocartilage. Many investigators have attempted to model CPPD crystal growth using both solution and a variety of gel systems. We have investigated the effect of type I collagen fibrils on CPPD crystal nucleation and growth using an ionic diffusion model. Collagen was isolated from porcine menisci using a pepsin solubilization procedure and gelled in three layers, with one containing 10 mM pyrophosphate (PPi) plus physiologic ions, the middle containing only the ions, while the third contained 25 mM Ca plus physiologic ions. Initially, amorphorous calcium pyrophosphate formed at the Ca-PPi interface. Monoclinic CPPD crystallized in 6 weeks when the [Ca] was between 2 and 3 mM and the [PPi] was between 50 and 75 μM. At 13 weeks, t-CPPD formed when the [Ca] was also between 2 and 3 mM, but the PPi was less than 25 μM. One of the most striking differences between this system and all previous solution and gel model systems is the total absence of orthorhombic calcium pyrophosphate tetrahydrate (o-CPPT) from the gels made of collagen fibrils in near native conformation. Further, crystals of t-CPPD appear as large single crystals with the classic prismatic growth habit observed in vivo, and crystals of m-CPPD also evidence the in vivo rod habit. In contrast, the crystal growth habits of t-CPPD, m-CPPD, and o-CPPT grown in all of the other model systems never matched that observed in vivo. When compared to the previous studies, these results, particularly the crystal growth habit data, suggest that the native collagen fibrils themselves can nucleate CPPD crystal formation.
Mandel, Gretchen S.; Halverson, Paul B.; Rathburn, Melisa; and Mandel, Neil S.
"Calcium Pyrophosphate Crystal Deposition: A Kinetic Study Using a Type I Collagen Gel Model,"
Scanning Microscopy: Vol. 4
, Article 18.
Available at: https://digitalcommons.usu.edu/microscopy/vol4/iss1/18