Association Between Crystals and Cartilage Degeneration in the Ankle

CAROL MUEHLEMAN, JUN LI, THOMAS AIGNER, LEV RAPPOPORT, ERIC MATTSON, CAROL HIRSCHMUGL, KOICHI MASUDA, and ANN K. ROSENTHAL

ABSTRACT.

Objective. Monosodium urate (MSU) and calcium pyrophosphate dihydrate (CPPD) crystals have been observed in synovial joints both before and after the onset of osteoarthritis (OA). The relationship between crystals and OA, however, remains controversial. We compared histologic and immunohistochemical patterns in articular cartilage of ankle joints with and without crystals.

Methods. A sample of 7855 human cadaveric tali was examined for the presence of surface and beneath-the-surface crystals. A random subsample of tali with and without crystals underwent crystal analysis by Fourier transform infrared spectroscopy (FTIR), histologic examination, and immunohistochemistry for S100 protein, superficial zone protein, collagen X, and cSRC.

Results. The prevalence of grossly visible crystals in the pool of donors over 18 years of age was 4.7% and correlated with advanced age, male sex, and obesity. Crystals were strongly associated with cartilage lesions and these lesions appeared to be biomechanically induced, being located where opposing articular surfaces might not be in congruence with each other. Thirty-four percent of the random subsamples of crystals upon which FTIR was performed contained CPPD, and the remainder were MSU crystals. Both crystal types were associated with higher levels of superficial zone protein and collagen X.

Conclusion. We show that the presence of surface crystals of either MSU or CPPD is strongly correlated with cartilage lesions in the talus. The histologic similarities in cartilage from joints with CPPD crystals compared to those with MSU crystals, together with what is known about the dramatically different etiologic factors producing these crystals, strongly suggest that these lesions are biomechanically induced. (First Release April 15 2008; J Rheumatol 2008;35:1108-17)

Key Indexing Terms:

ANKLE OSTEOARTHRITIS
GOUT
CALCIUM PYROPHOSPHATE DIHYDRATE
MONOSODIUM URATE CRYSTALS
TALUS
CARTILAGE

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From Rush University Medical Center, Chicago, Illinois; University of Wisconsin-Milwaukee; Medical College of Wisconsin, Milwaukee, Wisconsin, USA; and University of Leipzig, Leipzig, Germany.

Supported by National Institutes of Health grant NIAMS RO1 AR 40292-05.

C. Muehleman, PhD; J. Li, MD; L. Rappoport, MD; K. Masuda, MD, Rush University Medical Center; T. Aigner, MD, DSc, University of Leipzig; E. Mattson, BS; C. Hirschmugl, PhD, University of Wisconsin-Milwaukee; A.K. Rosenthal, MD, Medical College of Wisconsin.

Address reprint requests to Dr. C. Muehleman, Department of Biochemistry, Rush University Medical Center, Cohn Building, Room 524, 1735 W. Harrison St., Chicago, IL 60612. E-mail: carol_muehleman@rush.edu

Accepted for publication January 10, 2008.

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