Fig. 1

Upper left: in normal joints, most mesenchymal stem cells are resident cells from the synovium, but a small subset of bone marrow mesenchymal stem cells (BM-MSCs) can migrate from the bone into the synovium through canals of the bare zone areas [6]. Upper right: at the synovio-entheseal complexes, populations of BM cells can also invade the soft tissue side of the enthesis via holes in the subchondral bone plate [7]. Lower left: in RA, a small subset of epigenetically modified BM-MSCs from the subchondral bone marrow could migrate into the joint, this migration being enhanced by mechanical stretch [8]. BM-MSCs and their progeny can become pro-inflammatory (with secretion of interferon-gamma [9]), especially outside the bone marrow and when exposed to citrullinated fibrinogen [10]. In RA, those BM-MSCs express less A20 and secrete more IL-6 [11]. Their pro-inflammatory phenotype in RA synovitis could contribute to the typical erosions of this disorder, which occur in the bare zone areas, where BM-MSCs traffic from the bone into the synovium. Lower right: in SpA, the combined treatment of BM-MSC with IL-22, IFN-gamma, and TNF results in increased BM-MSC proliferation and migration [12]. The migration of epigenetically modified BM-MSCs in enthesis could contribute to inflammation, sometimes followed by ossification since BM-MSCs of AS patients have an intrinsic greater potential for osteogenic differentiation [13, 14], further enhanced by IL-22 secretion [12]