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ABSTRACT Osteoarthritis (OA) of the hand is a common disease resulting in pain and impaired function. The pathogenesis of hand OA (HOA) is elusive and models to study it have not been described. Chondrocyte culture has been essential to understand cartilage degeneration, which is a hallmark of OA. We investigated the feasibility of human chondrocyte culture derived from proximal interphalangeal (PIP) finger joints. Hyaline cartilage of the PIP and knee joints was obtained from human cadavers. Chondrocytes harvested up to 236 h after death of the donors were viable and expressed chondrocyte-specific genes. Gene expression comparing chondrocytes from PIP and knee joints using Affymetrix GeneChip arrays resulted in a unique PIP-specific gene expression pattern. Genes involved in developmental processes including the WNT pathway were differentially expressed between the joints. These findings suggest that our knowledge on chondrocyte biology derived mainly from knee and hip joints may not apply to chondrocytes of the PIP joints and some of the distinctive features of HOA may be caused by the specific properties of PIP chondrocytes. Chondrocyte culture of PIP cartilage is a novel tool to study cartilage degeneration in HOA. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1569-1575, 2016. [ABSTRACT FROM AUTHOR]