ABSTRACT
Rheumatoid arthritis (RA) and osteoarthritis (OA) are the two most common joint diseases, and they have characterization of synovial inflammation and cartilage destruction, associated with the accumulation of numerous catabolic mediators and inflammatory cells in the synovial space and surrounding soft tissues. How these factors are cleared and if the "clearance" process contributes to pathogenesis of arthritis are not known. Recently, we found the existence of the peri-articular lymphatic system in mouse joints. The blockade of lymphangiogenesis and lymphatic draining function accelerates while stimulation of lymphatic function attenuates the severity of joint tissue lesions in mouse models of RA and OA. More importantly, we noticed the similarity between the dysfunction of lymphatic drainage in arthritic joints and "Bi" theory of Chinese medicine (CM), and demonstrated that several Bi disease-treated herbal drugs directly affect the function of lymphatic endothelial cells. Here we review the advances about the interactions between joint inflammation and changes in the peri-articular lymphatic system and discuss our view of linking "Bi" theory of CM to lymphatic dysfunction in arthritis.
Subject(s)
Animals , Humans , Arthritis , Therapeutics , Disease Models, Animal , Joints , Pathology , Lymphangiogenesis , Lymphatic Vessels , Pathology , Medicine, Chinese TraditionalABSTRACT
Osteoclasts are derived from pluripotent stem cells in bone marrow and spleen.They play a critical role in inflammation-induced bone loss and joint destruction because in the absence of them,bone de- struction does not occur even when inflammation exists.Synovioblasts in an inflamed joint can secrete numerous inflammatory factors,including tumor necrosis factor alpha(TNF-?)and interleukin-1(IL-1)which not only induce inflammatory reactions but also elevate osteoclast formation and function indirectly or directly through promoting RANKL expression.In this wdy the inflammatory reactions are associated with bone loss and destruction. In this article,we focus on the recent progress in study of TNF-?,IL-1 and osteoclast-target therapies in management of osteoclast-mediated inflammatory bone loss.TNF-?promotes differentiation of osteoclast precursor cells in the peripheral blood and spleen,which causes a marked increase in mature osteoclasts in a diseased joint.However, IL-I supports osteoblast survival and regulates the recombination of osteoclast cytoskeleton,which further stimulates bone resorption.Since osteoclast-target therapies may inhibit osteoclast formation and function,they are becoming more and more important for inflammation-induced bone loss and joint destruction.