Stanford scientists found a way to regrow cartilage and stop arthritis

Stanford researchers report that blocking a protein called 15-PGDH - a gerozyme that rises with age and breaks down prostaglandin E2 - restores worn knee cartilage in aged mice, prevents osteoarthritis after ACL-like injuries, and induces regeneration of articular (hyaline) cartilage in human tissue samples. Administering a small-molecule 15-PGDH inhibitor systemically or directly into the joint thickened cartilage surfaces in old mice, reduced injury-driven osteoarthritis, and improved weightbearing and movement. Human cartilage taken during knee replacements began producing functional joint cartilage after one week of ex vivo treatment. An oral 15-PGDH inhibitor has already completed Phase 1 testing for muscle weakness and showed safety and activity in healthy volunteers, supporting the potential for a drug or injection to reduce the need for joint replacement if clinical trials confirm these effects.

Mechanistically, inhibiting 15-PGDH raises prostaglandin E2 and reprograms existing chondrocytes rather than recruiting stem cells: one degrader cell population fell from 8% to 3%, fibrocartilage-prone cells fell from 16% to 8%, and hyaline-producing chondrocytes rose from 22% to 42%. Treated tissues showed decreased expression of inflammatory and cartilage-degrading genes and increased extracellular-matrix and cartilage-development programs. Mouse and human-tissue results provide strong preclinical evidence, but targeted clinical trials are required to determine safety and efficacy for treating osteoarthritis in patients.