Osteoarthritis is a highly prevalent and debilitating joint disorder. There is no effective medical therapy for osteoarthritis due to limited understanding of osteoarthritis pathogenesis. We show that TGF–β1 is activated in the subchondral bone in response to altered mechanical loading in an anterior cruciate ligament transection (ACLT) osteoarthritis mouse model. TGF–β1 concentrations also increased in human osteoarthritis subchondral bone. High concentrations of TGF–β1 induced formation of nestin+ mesenchymal stem cell (MSC) clusters leading to aberrant bone formation accompanied by increased angiogenesis. Transgenic expression of active TGF–β1 in osteoblastic cells induced osteoarthritis. Inhibition of TGF–β activity in subchondral bone attenuated degeneration of osteoarthritis articular cartilage. Notably, knockout of the TGF–β type II receptor (TβRII) in nestin+ MSCs reduced development of osteoarthritis in ACLT mice. Thus, high concentrations of active TGF–β1 in the subchondral bone initiated the pathological changes of osteoarthritis, inhibition of which could be a potential therapeutic approach.
Numerous surgical procedures have been developed to correct patellar tracking and improve patellofemoral symptoms by altering the Q-angle (the angle between the quadriceps load vector and the patellar tendon load vector). The influence of the Q-angle on knee kinematics has yet to be specifically quantified, however. In vitro knee simulation was performed to relate the Q-angle to tibiofemoral and patellofemoral kinematics. Six cadaver knees were tested by applying simulated hamstrings, quadriceps and hip loads to induce knee flexion. The knees were tested with a normal alignment. after increasing the Q-angle and after decreasing the Qangle. Increasing the Q-angle significantly shifted the patella laterally from 20" to 60" of knee flexion, tilted the patella medially from 20" to 80" of flexion, and rotated the patella medially froin 20" to 50" of flexion. Decreasing the Q-angle significantly tilted the patella laterally at 20" and from 50" to 80" of flexion, rotated the tibia externally from 30" to 60" of flexion, and increased the tibiofemoral varus orientation from 40" to 90" of flexion. The results show that an increase in the Q-angle could lead to lateral patellar dislocation or increased lateral patellofemoral contact pressurles. A Q-angle decrease may not shift the patella medially, but could increase the medial tibiofemoral contact pressure by increasing the varus orientation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.