Gene expression and histological studies of articular chondrocytes in cam-type femoroacetabular impingement demonstrates chronic and sustained inflammation and age related abnormal extracellular matrix

Abstract

ABSTRACT: Introduction: Femoroacetabular impingement (FAI) is a frequent cause of hip pain associated with the degeneration of cartilage in hip joint. However, the molecular events linking the bone and cartilage deformation with joint degeneration are unclear. Objective: Using gene expression and histological analyses of cam-type FAI tissues to discover abnormal biological changes of chondrocytes that contribute to the molecular pathophysiology of FAI. Methods: Full-thickness cartilage specimens obtained from donors who underwent hip arthroscopy to address symptomatic cam-type FAI were analyzed. Quantitative real-time polymerase chain reaction (RT-PCR) was performed to assess gene expressions of markers for inflammation, extracellular matrix (ECM) synthesis, and cellular senescence. Histological specimens were prepared with safranin O/fast green staining as well as immunohistochemistry for evaluation. Results: Compared to normal cartilage, cam-type FAI tissues demonstrated decreased expression of ACAN, COL2, and Sox9. Additionally, chondrocytes in these tissues showed increased expressions of MMP13, ADAMTS4, and IL-1β, as well as p21, Bcl-2, and FasL. Histological analyses of the FAI tissues revealed two distinct phenotypes: safranin O positive (SO+) and negative (SO-) that demonstrated different stages of FAI related to patient age. Immunohistochemical studies of COL2, ACAN, MMP3, and PCNA showed differences between SO+ and SO- groups. Conclusions: Gene expression and histological analyses indicated that chronic and sustained inflammation and age related degradation of extracellular matrix associated with cell senescence were major characteristics of FAI tissue.

Keywords

• Femoroacetabular impingement
• Cartilage
• Cell senescence
• Osteoarthritis