Development of in vivo models of osteoarthritis and evaluation of exogenous glycosaminoglycans and non-strenuous exercise on osteoarthritic rat stifle joint: Histopathology, bone density, and expression of neuropeptides and their receptors.

摘要

The objectives of the study were to: (1) develop an osteoarthritis (OA) model in the rat and (2) evaluate the influence of a mixture of glycosaminoglycans (GAG) consisting of chondroitin sulfate (CS) [200 mg] and glucosamine HCl [250 mg], swimming, walking, and combined treatments on osteoarthritic rat stifle joints. Treatments were analyzed by histopathology, bone mineral density (BMD), and immunolocalization of substance P (SP), SP-receptor, beta-endorphin, and mu-receptor in the normal and OA joints as well as mRNA expression of pre-protachykinin and pro-opiomelanocortin (POMC), the genes that encode SP and beta-endorphin, respectively in the lumbar_2–5 dorsal root ganglia (DRG).; In the first project, rat stifle joints treated by either partial medial meniscectomy (PMM) (n = 7) or transection of the cranial cruciate ligament (n = 7) were compared with the untreated controls (n = 7) at 84 days post-surgery.; In the second project, rats were assigned to 9 groups: control (n = 7), sham-operation (n = 7), PMM (n = 9), PMM with saline (n = 9), PMM with GAG (n = 9), PMM with treadmill walking (n = 9), PMM with swimming (n = 9), PMM with treadmill walking and GAG (n = 9), PMM with swimming and GAG (n = 9).; Using dual X-ray absorptiometry, BMD was measured in the rat whole body and hindlimbs at the beginning, 6 weeks and 10 weeks post-surgery.; In conclusion, oral glucosamine and CS, treadmill walking, or swimming reduced lesions of articular cartilage in PMM treated rat stifles. Glucosamine and CS also reduced the intensity of synovitis which may be related to the decreased expression of the pre-protachykinin in DRGs. Increased POMC and pre-protachykinin in DRGs suggested that DRGs were additional sources of beta-endorphin and SP to the inflamed joints. Swimming may stimulate the production of SP and POMC by DRGs as evidenced by their higher expression compared to control and walking rats. Increased expression of SP-receptor in osteoarthritic chondrocytes suggests that SP has increased action on osteoarthritic cartilage. Amplification of pre-protachykinin in the synovium along with SP immunoreactive mast cells suggests that SP is locally produced, most likely by mast cells. (Abstract shortened by UMI.)