Pharmacotherapy: concepts of pathogenesis and emerging treatments. Novel targets in bone and cartilage.
The spectrum of arthritis ranges from erosive (e.g., rheumatoid arthritis) to ossifying disease with formation of new bone (e.g., ankylosing spondylitis and osteoarthritis). The molecular basis for these different patterns of arthritis had long been unclear. In the last few years, however, characterisation of catabolic and anabolic molecular pathways in different forms of arthritis led to a better understanding of joint remodelling and revealed novel therapeutic targets. Recent findings show that catabolic and anabolic molecular pathways govern bone and cartilage remodelling in healthy and arthritic joints. The predominance of catabolic molecular pathways (e.g., receptor activator of nuclear factor-kappaB ligand (RANKL)/RANK and cathepsin K) causes erosive disease whereas anabolic signalling (e.g., Wnt and fibroblast growth factor (FGF)18) favours the formation of new bone including bony spurs and subchondral sclerosis. Other pathways may have a dual function in arthritis (e.g., hedgehog) leading to either catabolic or anabolic joint remodelling dependent on other factors. Key mediators within these signalling pathways may serve as novel targets for treating pathological remodelling of bone and cartilage in arthritis. Molecular pathways govern remodelling processes of bone and cartilage in arthritic joints. Future therapies will likely target the pathologic activity of these molecular pathways to specifically block either catabolic or anabolic joint remodelling in arthritis.
Beyer
Christian
C
Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Krankenhausstrasse 12, 91054 Erlangen, Germany.
Schett
Georg
G
D048868:Adaptor Proteins, Signal Transducing; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001168:Arthritis / Q000188:drug therapy* / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D016723:Bone Remodeling / Q000187:drug effects* / Q000502:physiology; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D056657:Cathepsin K / Q000037:antagonists & inhibitors / Q000378:metabolism; D002986:Clinical Trials as Topic; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D005819:Genetic Markers; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D053245:RANK Ligand / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D018501:Antirheumatic Agents; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; D053823:Hedgehog Proteins; D053245:RANK Ligand; C422903:SOST protein, human; C505688:TNFSF11 protein, human; D051153:Wnt Proteins; C113569:fibroblast growth factor 18; D005346:Fibroblast Growth Factors; C534130:CTSK protein, human; D056657:Cathepsin K