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 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.