Welcome to the Boyce Lab
Our lab has had a long-term interest in the mechanisms whereby cytokines, hormones and growth factors regulate the formation, activation and survival of osteoclasts. In particular, we have studied the mechanisms whereby IL-1, TNF, PTHrP, RANKL, and TGFb affect these functions of osteoclasts using in vitro and in vivo models of bone resorption and common bone diseases, such as osteoporosis, metastatic bone disease, and inflammatory arthritis in collaboration with Lianping Xing and other members of the Center for Musculoskeletal Research at URMC. These studies have included exploring the roles of Src tyrosine kinase and NF-kB signaling in osteoclast activation and formation and demonstrating the requirement for Src in ruffled border formation, of TGFb in estrogen-induced osteoclast apoptosis, and of NF-kB p50 and p52 expression in osteoclast formation.
Recent studies are focused on the role of NF-kB canonical and non-canonical signaling in TNF- and RANKL- induced osteoclast formation and activation. Both of these cytokines activate NF-kB RelA and p50 in the canonical pathway to induce osteoclastogenesis, but they also induce expression of the NF-kB p100, an inhibitory protein that retains RelB in an inactive state in the cytoplasm and restricts signaling in the non-canonical pathway. We have found that unlike RANKL, TNF does not efficiently process p100 to p52 because it does not efficiently induce degradation RANK-associated TRAF3 to facilitate NIK-induced processing of p100. We have generated p100/RelB double knockout mice to explore the role of non-canonical NF-kB signaling in bone cell function and in hematopoietic stem cell functions. The RelB-/- and p100/RelB double knockout mice have increased bone mass and reduced HSC functions. The mechanisms involved are the subject of ongoing NIH-funded research.