Distinct Gene Expression Patterns in Surface, Middle, and Deep Zones of Bovine Articular Cartilage

Introduction The regeneration of articular cartilage remains a challenge and is an unmet clinical need in orthopaedic surgery. Since hyaline articular cartilage will not heal spontaneously, these lesions eventually lead to degenerative joint disease. Cartilage abrasion, subchondral drilling, and microfracture techniques stimulate articular cartilage healing by introducing endogenous “stem cells” from the bone marrow to the damaged area; however, they result in fibrocartilaginous healing and do not offer durable surgical repair.(1-3) The osteoarticular transfer system (OATS) harvest articular cartilage plugs with intact subchondral bone from a donor site and provide partial hyaline articular cartilage coverage to an area of damaged articular cartilage.(4-6) However, this technique has a significant challenges in terms of donor site morbidity, especially with large defects, and yields only fibrocartilaginous healing. Autologous chondrocyte implantation (ACI) expands harvested chondrocytes in vitro and reimplants them into an area of damaged articular chondrocytes under a periosteal flap.(7) Recently, allograft juvenile articular cartilage (deNovo NT, Zimmer, Inc., Warsaw, Indiana) has been utilized to avoid the technical requirements as well as donor site morbidity of ACI and OATS. However, this technology results in poor integration with recipient cartilage especially in the superficial zone.(8, 9) A complete understanding of the responsive cells, inductive signals, and extracellular scaffolding required for the recapitulation of embryonic development and morphogenesis (i.e., regeneration) remain elusive.(10-12) Our hypothesis is that distinct sets of gene expression defines the different zones of the articular cartilage. We have investigated gene expression patterns in the superficial, middle, and deep zones by microarray analysis of bovine articular cartilage in an attempt to better understand the gene expression patterns and determine potential signaling pathways for optimal articular cartilage regeneration and homeostasis.