Excess Growth Hormone Triggers Inflammation-Associated Arthropathy, Subchondral Bone Loss, and Arthralgia

Abstract

Growth hormone (GH) is a key mediator of skeletal growth. In humans, excess GH secretion due to pituitary adenoma, seen in patients with acromegaly, results in severe arthropathies. This study investigated the effects of long-term excess GH on the knee joint tissues. One year-old wild-type and bovine GH (bGH) transgenic mice were used as a model for excess GH. bGH mice showed increased sensitivity to mechanical and thermal stimuli, as compared to WT mice. Micro-CT analyses of the distal femur subchondral bone (SCB) revealed significant reductions in trabecular thickness, significantly reduced bone mineral density of the tibial SCB-plate, that were associated with increased osteoclast activity in both male and female bGH as compared to WT mice. bGH mice showed severe loss of matrix from the articular cartilage (AC), osteophytosis, synovitis, and ectopic chondrogenesis. AC loss in the bGH mice was associated with elevated markers of inflammation and chondrocyte hypertrophy. Finally, hyperplasia of synovial cells was associated with increased expression of Ki67 and diminished p53 levels in the synovium of bGH mice. Unlike the low-grade inflammation seen in primary osteoarthritis, arthropathy caused by excess GH affects all joint tissues, and triggers severe inflammatory response. Data of this study suggest that treatment of acromegalic arthropathy should involve inhibition of ectopic chondrogenesis, and chondrocyte hypertrophy.