Disruption of CXCR4 enhances osteoclastogenesis and tumor growth in bone

@article{citeulike:2425943, abstract = {CXCR4 regulates hematopoietic and tumor cell homing to bone, but its role during osteoclast (OC) development is unknown. We investigated the role of CXCR4 in osteoclastogenesis and in a model of bone metastasis. Compared with controls, mice reconstituted with CXCR4 null hematopoietic cells exhibited elevated markers of bone resorption, increased OC perimeter along bone, and increased bone loss. CXCR4/ OCs demonstrated accelerated differentiation and enhanced bone resorption in vitro. Furthermore, tumor growth specifically in bone was significantly increased in mice reconstituted with CXCR4/ hematopoietic cells. Finally, enhancement of bone tumor growth in the absence of CXCR4 was abrogated with the OC inhibitor, zoledronic acid. These data demonstrate that disruption of CXCR4 enhances osteoclastogenesis and suggest that inhibition of CXCR4 may enhance established skeletal tumor burden by increasing OC activity. 10.1073/pnas.0705203104}, author = {Hirbe, Angela C. and Rubin, Jessica and Uluckan, Ozge and Morgan, Elizabeth A. and Eagleton, Mark C. and Prior, Julie L. and Piwnica-Worms, David and Weilbaecher, Katherine N. }, citeulike-article-id = {2425943}, doi = {http://dx.doi.org/10.1073/pnas.0705203104}, journal = {Proceedings of the National Academy of Sciences}, keywords = {cxcl12}, month = {August}, number = {35}, pages = {14062--14067}, posted-at = {2008-02-25 16:12:59}, priority = {1}, title = {Disruption of CXCR4 enhances osteoclastogenesis and tumor growth in bone}, url = {http://dx.doi.org/10.1073/pnas.0705203104}, volume = {104}, year = {2007} }

TY - JOUR ID - citeulike:2425943 L3 - citeulike-article-id:2425943 TI - Disruption of CXCR4 enhances osteoclastogenesis and tumor growth in bone JF - Proceedings of the National Academy of Sciences VL - 104 IS - 35 SP - 14062 EP - 14067 N2 - CXCR4 regulates hematopoietic and tumor cell homing to bone, but its role during osteoclast (OC) development is unknown. We investigated the role of CXCR4 in osteoclastogenesis and in a model of bone metastasis. Compared with controls, mice reconstituted with CXCR4 null hematopoietic cells exhibited elevated markers of bone resorption, increased OC perimeter along bone, and increased bone loss. CXCR4/ OCs demonstrated accelerated differentiation and enhanced bone resorption in vitro. Furthermore, tumor growth specifically in bone was significantly increased in mice reconstituted with CXCR4/ hematopoietic cells. Finally, enhancement of bone tumor growth in the absence of CXCR4 was abrogated with the OC inhibitor, zoledronic acid. These data demonstrate that disruption of CXCR4 enhances osteoclastogenesis and suggest that inhibition of CXCR4 may enhance established skeletal tumor burden by increasing OC activity. 10.1073/pnas.0705203104 KW - cxcl12 AU - Hirbe, Angela AU - Rubin, Jessica AU - Uluckan, Ozge AU - Morgan, Elizabeth AU - Eagleton, Mark AU - Prior, Julie AU - Piwnica-Worms, David AU - Weilbaecher, Katherine PY - 2007/08/28/ UR - http://dx.doi.org/10.1073/pnas.0705203104 ER -