Potential role of bone marrow-derived stem cells in trafficking to the subchondral bone and synovial membrane in rheumatoid arthritis joints, resulting in a subchondral cellular infiltrate (seen as bone oedema on MRI) followed by erosion. (a) CD34+ stem cells from bone marrow express high levels of NFkB, which leads to unusual sensitivity to TNFα. (b) Stem cells differentiate into fibroblast-like cells and travel via the circulation to synovial membrane to become type B synoviocytes – here they mediate formation of erosions via production of proinflammatory cytokines and matrix metalloproteinases [23,25]. (c) Stem cells may also traffic to the subchondral bone marrow where they differentiate into mesenchymal cells. These cells could then travel via bony canals from bone marrow to synovium  to excite an inflammatory response. (d) Alternatively, stem cells could travel to subchondral bone and at this site could mediate an inflammatory response via T/B cell interactions associated with angiogenesis  and osteoclast activation. This could lead to erosions originating from inside the bone, directed outwards towards joint surface . (e) Coronal T2 weighted MRI scan of the wrist in early rheumatoid arthritis reveals bone oedema at the bases of the 2nd and 3rd metacarpals and adjacent regions of trapezoid and capitate carpal bones. Small intraosseous erosions are also apparent.
McQueen and Ostendorf Arthritis Research & Therapy 2006 8:222 doi:10.1186/ar2075