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Genome-wide expression analysis of intra- and extraarticular connective tissue.

ABSTRACT: In comparison to extraarticular ligaments and tendons, the intraarticular ligaments such as the anterior and posterior cruciates exhibit different biochemical, biomechanical, and viscoelastic properties and most importantly, differential abilities to heal after surgical repair. Little is known about the underlying basis for these differences, in large measure due to the paucity of molecular markers distinguishing different classes of tendons and ligaments. To date, there has been no systematic analysis of gene expression differences between different types of connective tissues. We used Affymetrix expression arrays to analyze the differences in gene expression levels between the anterior cruciate, posterior cruciate, and medial collateral ligaments, the patellar and Achilles tendons and the synovium. We have identified five clusters of gene cohorts displaying similar expression patterns. These clusters group into three categories including: (1) genes that are strongly expressed in all connective tissues compared to the synovium control tissue; (2) genes that distinguish intraarticular connective tissues from extraarticular connective tissues; and (3) a group of genes expressed in common by the patellar tendon and the synovium. Our analysis identifies a new marker of tendons and ligaments (fibin2), demonstrates molecular diversity between subtypes of tendons and ligaments, and indicates that the primary molecular subdivision among dense regular connective tissues is intra- versus extraarticular rather than ligament versus tendon.

SUBMITTER: Pearse RV

PROVIDER: S-EPMC2856484 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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Genome-wide expression analysis of intra- and extraarticular connective tissue.

Pearse Richard V RV Esshaki Diana D Tabin Clifford J CJ Murray Martha M MM

Journal of orthopaedic research : official publication of the Orthopaedic Research Society 20090401 4

In comparison to extraarticular ligaments and tendons, the intraarticular ligaments such as the anterior and posterior cruciates exhibit different biochemical, biomechanical, and viscoelastic properties and most importantly, differential abilities to heal after surgical repair. Little is known about the underlying basis for these differences, in large measure due to the paucity of molecular markers distinguishing different classes of tendons and ligaments. To date, there has been no systematic a ...[more]

PMID: 18972360

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Project description:BackgroundACL reconstruction aims to restore knee function and stability; however, rotational stability may not be completely restored by use of standard intraarticular reconstruction alone. Although individual studies have not shown the superiority of combined ACL reconstruction compared with isolated intraarticular reconstruction in terms of function and stability, biomechanical principles suggest a combined approach may be helpful, therefore pooling (meta-analyzing) the available randomized clinical studies may be enlightening.Questions/purposesWe performed a meta-analysis to determine whether combining extraarticular with intraarticular ACL reconstruction would lead to: (1) similar knee function measured by the IKDC evaluation, return-to-activity, and Tegner Lysholm scores, compared with isolated intraarticular reconstruction; (2) increased stability measured by pivot shift and instrumented Lachman examination; and (3) any differences in complications and adverse events?MethodsTo identify randomized controlled trials (RCTs) comparing combined intra- and extrarticular ACL reconstruction (combined reconstruction) with intraarticular ACL reconstruction only, we searched MEDLINE, EMBASE, SPORTDiscus, Latin American and Caribbean Health Sciences (LILACS), and the Cochrane Central Register of Controlled Trials, and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. The main outcomes we sought were patient function and stability and complications after ACL reconstruction. Of 386 identified studies, eight RCTs were included (n=682 participants; followup, 12-84 months; men to women ratio, 2.17:1) in our meta-analysis. Study quality (internal validity) was assessed using the Cochrane risk-of-bias tool; in general, we found a moderate quality of evidence of the included studies.ResultsWhen functional outcomes were compared, we found no difference between patients who underwent intraarticular ACL reconstruction only and those who underwent combined reconstruction (IKDC, return-to-activity, and Tegner Lysholm scores). However, patients who underwent combined reconstruction were more likely to show improved stability based on the pivot shift test (risk ratio [RR], 0.95; 95% CI, 0.91-0.99; p=0.02) and Lachman test (RR, 0.93; 95% CI, 0.88-0.98; p=0.01). In addition, our meta-analysis found no difference between the two treatments in terms of general complications or adverse events (RR, 1.31; 95% CI, 0.70-2.34; p=0.40) and the proportion of patients whose reconstructions failed (RR, 2.88; 95% CI, 0.73-11.47; p=0.13).ConclusionCombined intra- and extraarticular ACL reconstruction provided marginally improved knee stability and comparable failure rates but no difference in patient-reported functional outcomes scores. Complications and adverse events such as knee stiffness may be underreported and technical factors such as graft placement were difficult to evaluate. Future studies are needed to determine whether the small differences in additional stability warrant the potential morbidity of the additional extraarticular procedure and to determine long-term failure rates.

Dataset Information

Genome-wide expression analysis of intra- and extraarticular connective tissue.

Publications

Genome-wide expression analysis of intra- and extraarticular connective tissue.

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