Transforming growth factor beta 1 (TGFβ1), a peptide involved in many aspects of cell function, could play a role in bone remodeling and OA, Dr. Cao said. In TGFβ1-knockout mice, bone remodeling and bone formation are decreased, and the proteins cannot migrate mesenchymal stem cells (MSCs) to the bone site. In wild-type mice with TGFβ1, stem cell migration to bone surfaces is normal, he said.
If a large amount of TGFβ1 is released by subchondral bone, which can occur during mechanical loading, it may result in bone resorption and knee OA, Dr. Cao said. Abnormal mechanical stress on a joint triggers the bone to respond and release TGFβ1, which recruits stem cells that in turn may lead to aberrant bone formation and, possibly, angiogenesis.
High levels of active TGFβ1 induce an increase in MSCs and initiate abnormal bone formation and angiogenesis at the onset of OA, Dr. Cao said.
OA therapy research targets molecules that inhibit TGFβ1, including halofuginone, used as an antimalarial treatment in Chinese medicine. Halofuginone inhibits angiogenesis and the development of T-helper 17 cells that play an important role in autoimmunity, Dr. Cao said. It can also prevent articular cartilage degeneration in joints with anterior cruciate ligament tears, and help attenuate OA progression.
Susan Bernstein is a freelance medical journalist based in Atlanta.