Osteoarthritis is considered an illness in which a complex interaction between the tissues of the joint plays a significant role in the initiation and/or progression of this pathophysiology. We do not yet completely understand all the factors that are responsible for initiating the degradation and loss of the articular tissues. This paper summarizes the novelties of three such mechanisms. The first one points to some factors involved in the regulation of one growth factor family, the bone morphogenetic proteins, the second, the regulation of prostaglandin E(2) synthesis, and the third the factors involved in subchondral bone remodeling, all of which could be very significant events for osteoarthritis. This paper should help the reader better understand the most recent advances regarding the roles of these factors in this disease process, and how new therapeutic targets may be identified.