Mechanical Loading Alleviates The Pathological Progression Of Osteoarthritis

BackgroundOsteoarthritis is a chronic joint disease characterized by cartilage degradation,abnormal remodeling of subchondral bone,synovial inflammation and osteophyte formation.OA affects 150 million people worldwide.In the United States,about 37% of people over the age of 60 have osteoarthritis.Risk factors for OA include age,obesity,joint trauma,and heredity.Current treatments for OA include early non-pharmacological treatments,medical treatments,and advanced surgical treatments,but none of them are effective in treating OA.Mechanical loading as a new type of physical rehabilitation treatment,which is a lateral joint loading mode that affects bone metabolism by imparting a mild,low-frequency stimulus to the synovial joint to alter fluid flow in the medullary cavity.Our previous research has demonstrated that mechanical joint loading can induce bone formation and accelerate the healing of injured bones.Pulsed joint mechanical loading can be performed for various synovial joints in the form of elbow joint loading and knee joint loading.Previous work has also shown that mechanical joint loading can increase the thickness of the cortical bone of long bones,especially mechanical knee loading can induce anabolic reactions,prolong the femur and tibia,accelerate the healing of surgical wounds,and treat femoral head necrosis.Previous work has also shown that mechanical joint loading can reduce matrix metalloproteinase 13(MMP-13)activity in cartilage.In general,the principle of mechanical loading is to activate the anabolic gene in the bone by changing the intramedullary pressure of the bone marrow cavity and causing the load-driven pressure to generate fluid flow in the lacunar tubule network of the cortical bone.Our previous studies have also shown that mechanical knee loading can repair the damage of early cartilage and subchondral bone.ObjectiveOur group established a model of osteoarthritis with medial joint instability(DMM)to comprehensively observe the medial knee cartilage,subchondral bone,synovium and osteophyte at three different time points after 2,4,and 8 weeks of osteoarthritis surgery,and the therapeutic effects of mechanical loading on them.In addition,we also observed the pathological changes of the cartilage and subchondral bone of the lateral knee joint and the therapeutic effect of mechanical loading.MethodsExperiment 1: 20 female C57BL/6 mice(~14-week-old)were randomly divided into normal control group(Control,n=5),2-week OA group(2wOA,n=5),and 4-week OA group(4wOA,n=5),8-week OA group(8wOA,n=5).The medial meniscus was removed to establish an animal model of osteoarthritis.The pathological changes of the knee joints of the mice at three time points were observed by H&E staining to estimate whether the modeling was successful.Experiment 2: 54 female C57BL/6 mice(~14-week-old)were divided into the sham operation group(control),OA group,and OA+loading group(OAL)by a random number table method.Each group was divided into 2-,4-and 8-week sub-groups(n = 6).H&E and Safranin O/fast green staining were used to observe changes in the medial and lateral knee cartilage and subchondral bone,as well as the therapeutic effect of mechanical loading on synovial inflammation and osteophyte formation.Changes in osteoclast and osteoblast activity in subchondral bone were observed using tartrate-resistant acid phosphatase(TRAP)and MacNeal's staining,respectively.ResultsThe results showed that in both medial and lateral sides,knee loading significantly increased articular cartilage thickness,and improved the OARSI scores,synovial,and osteophyte scores.Knee loading also improved changes of SBP and B.Ar/T.Ar in subchondral bone.Notably,the lesions of the medial and lateral sides were severely developed in 4 and 8 weeks respectively,and the loading effect was most observed at each of those time points.The correlation analysis showed the change among cartilage,subchondral bone,synovium,and osteophyte were positively correlated.The osteoclasts and osteoblasts activities in subchondral bone were both regulated by knee loading.ConclusionsThis study demonstrates that knee loading can attenuate the pathological progression of OA whole joint which associated with bone remodeling of subchondral bone,and indicates its potential clinical use as an adjuvant therapy.