21 – HUMAN MALE ELBOW JOINT CAPSULE MOLECULAR PROFILES IN PRIMARY OSTEOARTHRITIS AND POST-TRAUMATIC CONTRACTURES

Abstract

Purpose: Elbow osteoarthritis (OA) is characterized by a loss of elbow motion secondary to joint capsular hypertrophy and osteophyte formation. Previous work on joint capsules in post-traumatic (PT) elbow joint contractures has shown that alterations in cell populations (increased number of alpha-SMA positive myofibroblasts), matrix molecule and enzyme, and growth factor mRNA profiles are associated with loss of elbow motion in this condition. The objective of this study was to determine whether alterations in joint capsule parameters were similar or different in two etiologies of human elbow contractures, primary OA and PT.

Method: Posterior elbow joint capsules were obtained from eight male patients with primary elbow OA (age 52±12 yr ), five male patients with chronic (> 1 year) PT (age 47±12 yr ) and four male organ donors free of OA and contractures (age 43±10 yr ). RNA was extracted for subsequent real-time PCR for alpha-SMA, interleu-kin-1beta, MMP-1, MMP-3, collagen type III, biglycan, versican, tenascin C, TIMP-1, MMP-2, iNOS, COX-2, glyceraldehyde – 3 phosphate dehydrogenase (GAPDH) and 18S. 18S was used to normalize gene expression. Statistical comparisons used a oneway ANOVA followed by posthoc Tukey test. Significance was p < 0.05.

Results: The mRNA levels in the OA and PT capsules were increased compared to controls in most cases. This includes the major matrix molecule collagen I and the myofibroblast marker alpha-SMA, the growth factors TGF-beta1 and CTGF plus decorin, the injury response elements (collagen III, biglycan, versican, tenascin C) as well as TIMP-1 and MMP-2. The housekeeping gene GAPDH was similar in all 3 groups as was COX-2, while iNOS was elevated in both groups characterized by contractures. When comparing the two contracture groups, the mRNA levels were similar for some molecules while differences were evident in other instances. In PT, alpha-SMA and collagen I were greater than in OA. Conversely, in the OA group, the growth factors and matrix enzyme systems exhibited higher levels than PT.

Conclusion: In this study of human elbow joint capsules, we have shown that relative mRNA levels for markers of myofibroblasts, major matrix components, injury response elements and selected growth factors are significantly elevated in elbow OA and post-traumatic contractures when compared to age matched organ donor controls free of contractures. When comparing the OA and PT groups, the injury response molecules were elevated to similar relative levels. The OA group had greater increases in the growth factors and many of the matrix enzymes / inhibitors measured, while the PT group had greater increases in the myofibroblast marker alpha-SMA and the major matrix molecule collagen I. Thus in general matrix, growth factor and cellular properties appear to be preferentially altered in the two conditions studied when compared to control tissues, strengthened by the fact that the housekeeping gene GAPDH had similar relative levels in all 3 groups.