Brief Report: Distinct Dysregulation of the Small Leucine‐Rich Repeat Protein Family in Osteoarthritic Acetabular Labrum Compared to Articular Cartilage

Abstract

Objective. Articular cartilage is well studied in osteoarthritis (OA). However, the role of supporting structures, such as the acetabular labrum, a sealing structure surrounding the hip joint, has been investigated much less. We recently showed that fibrochondrocytic labrum cells are metabolically active. This study was undertaken to investigate hip OA-associated changes in human acetabular labrum cells.Methods. Microarray analysis was performed to compare OA labrum cells to healthy labrum cells cultured in a 3-dimensional alginate bead system. Data were analyzed by cluster analysis using gene set enrichment analysis software and by gene list analysis using PANTHER gene family tools. Selected candidates were validated by quantitative polymerase chain reaction analysis on labrum and cartilage samples and by immunohistochemistry. The functional impacts of the genes identified were investigated by in vitro stimulation experiments in labrum cells.Results. Pathway analysis revealed increased cytokine and chemokine signaling in OA labrum cells, whereas reduced extracellular matrix interactions and transforming growth factor ␤ signaling were observed. Several genes were significantly differentially expressed in OA compared to healthy labrum. We specifically focused on 3 small leucine-rich repeat proteins (SLRPs), osteomodulin, osteoglycin, and asporin, that appeared to be distinctly regulated in OA labrum compared to OA cartilage. SLRPs were strongly downregulated in OA labrum but up-regulated in OA articular chondrocytes. Moreover, in vitro stimulation with osteomodulin increased aggrecan expression in OA labrum cells.Conclusion. OA labrum fibrochondrocytes have several features similar to OA chondrocytes. However, SLRP expression seems to be differentially influenced by degeneration in OA labrum compared to cartilage, suggesting a specific role for this supporting structure in OA. The functional impact of SLRPs on labrum cells makes them interesting targets for further studies in hip OA.

Comparison of secretome from osteoblasts derived from sclerotic versus non-sclerotic subchondral bone in OA: A pilot study

“…OMD, also called osteoadherin, is an extracellular matrix keratan sulfate proteoglycan member of the small leucine-rich repeat protein family. It was thought to be bone specific but recently OMD expression was found in articular chondrocytes and labrum-derived fibrochondrocytes [ 20 ]. Little is known about the biological activity of OMD.…”

The diverse functions of osteoglycin: a deceitful dwarf, or a master regulator of disease?

“…Moreover, OGN was shown to be a protein released in osteoarthritic articular cartilage in humans (77). It has also been found in synovial fluid of patients with osteoarthritis (78) and has been demonstrated to be up‐regulated in articular cartilage, yet down‐regulated in the acetabular labrum of patients with osteoarthritis (79). Furthermore, low‐level laser therapy, which is often used in the treatment of rheumatoid arthritis, increased OGN expression, both in the synovial membrane of patients (80), and in cultured osteoblasts (46).…”

Labral calcification in end‐stage osteoarthritis of the hip correlates with pain and clinical function

“…The labral fibrocartilage of the hip may deserve further study in this context. Recently, it was demonstrated that labrum cells are metabolically active fibrochondrocytes similar to meniscal chondrocytes, which are capable of producing proinflammatory cytokines and react to proinflammatory stimuli that can drive cartilage degeneration . In addition, it is well known that OA in general is associated with ectopic cartilage calcium crystal deposition .…”

“…Recently, it was demonstrated that labrum cells are metabolically active fibrochondrocytes similar to meniscal chondrocytes, which are capable of producing proinflammatory cytokines and react to proinflammatory stimuli that can drive cartilage degeneration. 19,20 In addition, it is well known that OA in general is associated with ectopic cartilage calcium crystal deposition. [21][22][23][24][25] As such, cartilage calcification (CC) of the hyaline cartilage is detectable in 100% of hip and knee joints with endstage OA.…”