Differential proteome of bone marrow mesenchymal stem cells from osteoarthritis patients

Abstract

Adult mesenchymal stem cells (MSCs) are multipotent cells whose primary reservoir is bone marrow (BM). Following situations of extensive tissue damage, MSCs are mobilized and migrate to the site of injury. Osteoarthritis (OA) is a condition that involves extensive cartilage and bone damage. To gain insight into the pathogenesis of OA, we have analyzed the differential BM-MSCs proteome of OA patients. MSCs protein extracts were prepared from BM aspirates from six patients with OA and from six hip fracture subjects without OA, and analyzed by Two-dimensional gels, using the differential in-gel electrophoresis approach. Differentially expressed proteins were identified by mass spectrometry. In addition, the chemotactic responses of OA and control MSCs were assessed. The majority of proteins that changed at least 1.5-fold (P<0.05) belonged to the following three categories: metabolic enzymes (14 proteins, 36%), cytoskeleton/motility (12 proteins, 32%), and transporters (three proteins, 8%). In OA MSCs, a high percentage of metabolic enzymes (n=8, 57%) were up-regulated and most of the proteins related to cytoskeleton/motility (n=9, 75%) were down-regulated. There was a significant increase in the migration response of OA MSCs to platelet-derived growth factor-BB (chemotaxis index CI: 5.13+/-1.19 vs 3.35+/-0.42, P=0.043). In this study, we have described the differential proteome of BM-MSCs from OA patients together with an increased chemotactic response of these cells in the context of OA. These results could indicate an activation of OA BM-MSCs in response to chemotactic signals sent by the altered subchondral bone in an attempt to heal damaged tissue.