Figure 7. One hypothetical mechanism for the regulation of osteoclast formation during estrogen deficiency points to a crucial role of TNF--producing T-cells. Experimental observations in mice have shown that estrogen deficiency results in decreased expression of TGF-ß, which leads to enhanced expression of IFN- and subsequent augmented expression of class II transactivator in macrophages. This eventually causes increased numbers of TNF--producing T-cells. Thus, lack of TNF- signaling makes mice resistant to ovariectomy-induced increased osteoclastogenesis, similar to observations in mice lacking INF- signaling.