TY - JOUR
T1 - Disruption of CXCR4 enhances osteoclastogenesis and tumor growth in bone
AU - Hirbe, Angela C.
AU - Rubin, Jessica
AU - Uluçkan, Özge
AU - Morgan, Elizabeth A.
AU - Eagleton, Mark C.
AU - Prior, Julie L.
AU - Piwnica-Worms, David
AU - Weilbaecher, Katherine N.
PY - 2007/8/28
Y1 - 2007/8/28
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 osteoclasto-genesis and suggest that inhibition of CXCR4 may enhance established skeletal tumor burden by increasing OC activity.
AB - 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 osteoclasto-genesis and suggest that inhibition of CXCR4 may enhance established skeletal tumor burden by increasing OC activity.
KW - Bone metastasis
KW - Osteoclast
UR - http://www.scopus.com/inward/record.url?scp=35348884254&partnerID=8YFLogxK
U2 - 10.1073/pnas.0705203104
DO - 10.1073/pnas.0705203104
M3 - Article
C2 - 17715292
AN - SCOPUS:35348884254
SN - 0027-8424
VL - 104
SP - 14062
EP - 14067
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 35
ER -