Noggin, an inhibitor of bone morphogenetic protein signaling, antagonizes TGF-ß1 in a mouse model of osteoarthritis.

Osteoarthritis (OA) is the most common joint disease worldwide; however, disease-modifying treatments are lacking because of the complicated pathological mechanisms. As a breakthrough, aberrant activation of transforming growth factor-ß 1 (TGF-ß1)in subchondral bone has been confirmed as an essential pathomechanism for OA progression, and has become a potential therapeutic target. In addition to R&D on neutralizing antibodies, small-molecule antagonists and chemical medicines, native antagonists of TGF-ß1 could be exploited as another promising approach. Noggin (NOG) is an antagonist of bone morphogenetic proteins (BMPs) and was reported to effectively attenuate OA by protecting cartilage and preventing pathological subchondral bone remodeling. However, the underlying mechanisms have not been fully clarified. We first detected the distribution of NOG in knee joints of an OA mouse model, which showed upregulation at early stage of OA but downregulation later in the subchondral bone and no significant change in the articular cartilage. Furthermore, the interaction between NOG and TGF-ß1 was verified, which in turn suppressed the downstream SMAD2/3 activity of TGF-ß1. Moreover, the proliferation and chondrogenesis of mesenchymal stem cells (MSCs) were not significantly influenced by NOG. Taken together, the results showed that NOG antagonized TGF-ß1 but did not repress MSC proliferation and chondrogenesis; thus, it seems promising for OA treatment.