gms | German Medical Science

Objectives: The lipid profile of synovial fluid (SF) is related to the health status of articular joints. Early stages of human osteoarthritis (eOA) are not well understood because of a lack of samples availability for research. OA animal models have been developed to gain insights into the pathophysiology of OA progression. This study investigates whether the canine groove model of OA resembles more the early or late stages of human OA based on the changes to the SF lipid species profile. Furthermore, the SF lipidomes of humans, dogs and horses were compared to identify the mammalian species which more closely reflects the normal human lipid species profile.

Methods: Lipids were extracted from cell- and cellular debris-free knee SF obtained from 9 joint-healthy donors, 17 patients with early and 13 patients with late (lOA) osteoarthritic changes, nine dogs with knee OA and contralateral healthy joints, and from 14 horses with healthy knees. Lipids were quantified using electrospray ionization tandem mass spectrometry. Statistically significant differences in lipid concentrations between control and OA canine SF were determined by paired t-test of the log-values. Differences between the three cohorts were determined using analysis of variance (ANOVA). P-values of less than 0.05 were considered to represent statistical significance. The present study was approved by the ethical review committee of our University.

Results and Conclusion: Compared to control canine SF most of the determined lipid classes were elevated in canine OA SF. The total lipid content was elevated 2.6-fold in the canine OA SF (375 nmol/ml) compared to controls (147 nmol/ml). Of the 389 individual lipid species that were analyzed, 50 different lipid species belonged to the three major lipid classes phosphatidylcholine (30), lysophosphatidylcholine (6), and sphingomyelin (14). Remarkably, when compared to canine control SF a total of 34 different lipid species were found to be at higher levels in canine OA SF. Moreover, the lipid species profiles from the OA canine model resembled more closely the human eOA SF profile.

Compared to normal human SF, many lipids were often present at higher levels in control canine SF but at lower levels in normal equine SF. Interestingly, levels of certain lipid species from the phosphatidylcholine and lysophosphatidylcholine class are altered in a way that is characteristic for the investigated mammalian species with respect to saturation and chain length of fatty acids.

Our lipidomic analysis is the first study which compares a broad spectrum of phospholipid and sphingolipid species present in human, canine, and equine SF. Our quantitative data reveals that the SF of the canine groove model of OA closely resembles the early osteoarthritic changes found in humans. Furthermore, normal equine and canine SF lipidome often reflect the normal human lipid metabolism.