Dynamic Subchondral Bone Changes in Murine Models of Osteoarthritis

‘Arthritis’ is a generic term which includes many different rheumatic disease types, all of which are connected with impaired functioning of joints. Osteoarthritis (OA) is the most common form of arthritis, and the leading cause of chronic disability in the Western world. In OA normal functioning of a joint becomes impaired. Movement of the joint is painful and limited, and in advanced disease stages patients may complain of nocturnal or permanent pain. In a diarthrodial joint, the ends of two bones meet, marked by a bony end plate called the subchondral bone plate. To provide frictionless movement, the subchondral bone plate is covered with a smooth surface of articular cartilage. Cartilage also acts as a shock absorber of mechanical forces and distributes the stresses more evenly on the underlying tissues. For joint lubrication, lubricin and hyaluronic acid are produced by the synovium and by the superficial layer of the articular cartilage. Menisci, tendons and ligaments firmly hold the two bones in place, and the surrounding musculature ensures that the bones are able to move with respect to each other. These latter structures also play an important role in shock absorption to protect the joint from excessive mechanical forces

ADAMTS5-/- mice have less subchondral bone changes after induction of osteoarthritis through surgical instability : implications for a link between cartilage and subchondral bone changes

SummaryObjectiveOsteoarthritis (OA) is characterized by damaged articular cartilage and changes in subchondral bone. Previous work demonstrated aggrecanase-2 deficient (ADAMTS5−/−) mice to be protected from cartilage damage induced by joint instability. This study analyzed whether this protective effect on cartilage is also reflected in the subchondral bone structure.MethodsRight knee joints from 10-week old male wild type (WT) and ADAMTS5−/− mice received transection of the medial meniscotibial ligament to induce OA, whereas left knees were left unoperated. After 8 weeks knee joints were scanned by micro-CT. The proximal tibia was selected for further analysis. Histology was performed to evaluate cartilage damage and osteoclast presence.ResultsADAMTS5−/− joints had a significantly thinner subchondral plate and less epiphyseal trabecular bone compared to WT joints. Histology confirmed previous findings that ADAMTS5−/− mice have significantly less cartilage damage than WT in the instability-induced OA model. Although the subchondral bone plate became significantly thicker at the medial tibial plateau in operated joints of both genotypes, the percentage increase was significantly smaller in ADAMTS5−/− mice (WT: 20.7±4.7%, ADAMTS5−/−: 8.3±1.2% compared to the left unoperated control joint). In ADAMTS5−/− animals a significant decrease was found in both Oc.N./BS and Oc.S./BS. Finally, in WT but not in ADAMTS5−/− mice a significant correlation was found between medial subchondral bone plate thickness and cartilage damage at the medial tibial plateau.ConclusionADAMTS5−/− joints that were protected from cartilage damage showed minor changes in the subchondral bone structure, in contrast to WT mice where substantial changes were found. This finding suggests links between the process of cartilage damage and subchondral bone changes in instability-induced OA

Statins and fibrates do not affect development of spontaneous cartilage damage in STR/Ort mice

Pathophysiology and treatment of rheumatic disease