The present invention relates to the identification and use of protein expression profiles with clinical relevance to osteoarthritis (OA). In particular, the invention provides the identity of marker proteins whose expressions are correlated with OA, OA subtype, and/or OA progression. Methods and kits are described for using these protein expression profiles in the study and/or diagnosis of OA, in the determination of the degree of advancement of OA, and in the selection and/or monitoring of treatment regimens. The invention also relates to the screening of drugs that modulate expression of these proteins or nucleic acid molecules encoding these proteins, in particular for the development of disease-modifying OA agents.