HMGB1 and arthritic joint disease: During arthritis genesis, apart from excessive osteoclast activities induced by upregulated factors such as IL-1β, TNF-α, IL-6, and HMGB1, in chondrocytes,453,454 TGF-β-mediated type H vessel invasion and Th17 differentiation in the subchondral microenvironment also contribute to arthritis progression.455–457 Intraperitoneal injection of TGF-β1R inhibitors attenuated chondrocyte apoptosis and cartilage degradation with decreased type H angiogenesis and osteoclast activities in subchondral bone of OA rat models.