Casticin attenuates early osteoarthritis progression by inhibiting subchondral bone destruction

Abstract

Objectives \nTo investigate whether osteoarthritis (OA) progression can be delayed by casticin in rodent models of anterior cruciate ligament transection (ACLT). \n \n \nMethods \nEighteen 2-month-old male C57BL/6J mice were randomised into 3 even groups (n=6) subjected respectively to sham-operation, ACLT-vehicle-treatment and ACLT-casticin-treatment. The knee capsule was dissected in the sham-operation group and ACLT on the right knee was conducted in the ACLT-vehicle-treatment and ACLT-casticin-treatment groups. Intragastric administration of the same amount of Tween-80 solution was conducted for the sham-operation and ACLT-vehicle-treatment groups; Intragastric administration of casticin of 20 mg/kg was conducted once per day for the ACLT-casticin-treatment group. Bone micro CT (μCT) was quantitated to detect alterations in microarchitecture of femoral condyle subchondral bone. Tartrate resistant acid phosphatase(TRAP) stain and NOX4 immunostaining were conducted to detect relative proteins and the osteoclast changes on the subchondral bone. Articular cartilage degeneration was graded using HE and safranin O-green staining and the Mankin score criteria. \n \n \nResults \nCompared with the the sham-operation group, the subchondral bone density, trabecular bone volume fraction and trabecular thickness were decreased, and the trabecular space, positive rates of TRAP stain and NOX4 immunostaining and Mankin scores were increased in the ACLT-vehicle-treatment group. All the above comparisons were statistically significant (P<0.05). Compared with ACLT-vehicle-treatment group, the subchondral bone density and trabecular bone volume fraction were increased, and the trabecular space, positive rates of TRAP stain and NOX4 immunostaining and Mankin scores were decreased in the ACLT-casticin-treatment group. All the above comparisons were statistically significant (P<0.05). \n \n \nConclusion \nAs casticin may attenuate early OA progression by inhibiting NOX4 activity in subchondral bone and formation of osteoclasts, it may be a new clue to preventive therapy for OA. \n \n \nKey words: \nOsteoarthritis, knee;\xa0Arthroplasty, subchondral;\xa0Anterior cruciate ligament;\xa0Casticin;\xa0Experimental study