Gene Expression in Glenoid Articular Cartilage Varies Across Acute Instability, Chronic Instability, and Osteoarthritis

Abstract

Background: Shoulder instability is a common pathology associated with an elevated risk of osteoarthritis (OA). Little is known about gene expression in the cartilage of the glenohumeral joint after dislocation events, particularly as it relates to the risk of posttraumatic OA. This study tested the hypothesis that gene expression in glenoid cartilage varies among acute instability (<3 dislocations), chronic instability ( ‡3 dislocations), and OA.Methods: Articular cartilage was collected from the anteroinferior glenoid of consenting patients undergoing shoulder stabilization surgery (n = 17) or total shoulder arthroplasty (n = 16). Digital quantitative polymerase chain reaction was used to assess the relative expression of 57 genes (36 genes from OA risk allele studies, 21 genes from differential expression studies), comparing (1) OA versus instability (acute and chronic combined), (2) acute versus chronic instability, (3) OA versus acute instability, and (4) OA versus chronic instability.Results: The expression of 11 genes from OA risk allele studies and 9 genes from differential expression studies was significantly different between cartilage from patients with instability and those with OA. Pro-inflammatory genes from differential expression studies and genes from OA risk allele studies were more highly expressed in cartilage in the OA group compared with the instability group, which expressed higher levels of extracellular matrix and pro-anabolic genes. The expression of 14 genes from OA risk allele studies and 4 genes from differential expression studies, including proinflammatory genes, anti-anabolic genes, and multiple genes from OA risk allele studies, was higher in the acute instability group compared with the chronic instability group. Cartilage in the OA group displayed higher expression of CCL3, CHST11, GPR22, PRKAR2B, and PTGS2 than cartilage in the group with acute or chronic instability. Whereas cartilage in both the acute and chronic instability groups had higher expression of collagen genes, cartilage in the OA group had expression of a subset of genes from OA risk allele studies or from differential expression studies that was lower than in the acute group and higher than in the chronic group.Conclusions: Glenoid cartilage has an inflammatory and catabolic phenotype in shoulders with OA but an anabolic phenotype in shoulders with instability. Cartilage from shoulders with acute instability displayed greater (cellular) metabolic activity compared with shoulders with chronic instability.Clinical Relevance: This exploratory study identified genes of interest, such as CCL3, CHST11, GPR22, PRKAR2B, and PTGS2, that have elevated expression in osteoarthritic glenoid cartilage. These findings provide new biological insight into the relationship between shoulder instability and OA, which could lead to strategies to predict and potentially modify patients' risk of degenerative arthritis due to shoulder instability. O steoarthritis (OA) of the glenohumeral joint affects up to 30% of adults over the age of...

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“…For example, a higher level of PRKAR2B was observed in the cartilage of patients with osteoarthritis compared with those with acute or chronic instability. 32 PRKAR2B has also been linked to the diagnosis/prognosis of type 2 diabetes, 33 chronic obstructive pulmonary disease, 34 and hypertension. 35 …”

Periostin Is a Biomarker for Anterior Shoulder Instability: Proteomic Analysis of Synovial Fluid

“…They found that POSTN had a higher expression in articular cartilage of shoulders with acute instability compared with shoulders with osteoarthritis. 1 Interestingly, tandem mass spectrometry identified POSTN as a significant protein of interest in the glenohumeral joint of patients with anterior shoulder instability. This begs the question of what is similar about the injury-specific factors between ACL tears and anterior shoulder dislocations.…”

Shoulder & Elbow

“…To accomplish this, a team from St Louis (Missouri, USA) collected articular cartilage from the anteroinferior glenoid of 17 consenting patients who were undergoing shoulder stabilization surgery, and 16 undergoing total shoulder arthroplasty. 3 Digital quantitative polymerase chain reaction was used to assess the relative expression of a panel of 57 candidate genes. These were selected as 36 from OA risk allele studies, and 21 from differential expression studies which compared OA to acute and chronic instability.…”