TNF and rheumatoid arthritis: However, a recent report shows that TNF-polarized macrophages (TPMs) produce insulin-like 6 peptide (INSL6) and Jagged1 to stimulate bone formation, slowing down bone loss caused by enhanced bone resorption in RA [144], which explains why anti-TNF therapy has a limited effect in improving the lost bone in patients with RA [145,146,147].