In contrast, TGFβ1 released by increased numbers of TCNs in BM during aging degrades TRAF3 in MPCs and this leads to increased NF-κB RelA/RelB-induced transcription of Tnfsf11 (encodes RANKL) and Ccl5. As a result, TCN numbers increase in BM during aging and cause osteoporosis in male mice by stimulating RANKL-induced resorption and inhibiting bone formation in a self-amplifying feedback loop (Fig. 9). Here, TRAF3 is linked to osteoporosis.