Long bone structure and strength depend on BMP2 from osteoblasts and osteocytes, but not vascular endothelial cells.
The importance of bone morphogenetic protein 2 (BMP2) in the skeleton is well known. BMP2 is expressed in a variety of tissues during development, growth and healing. In this study we sought to better identify the role of tissue-specific BMP2 during post-natal growth and to determine if BMP2 knockout affects the ability of terminally differentiated cells to create high quality bone material. We targeted BMP2 knockout to two differentiated cell types known to express BMP2 during growth and healing, early-stage osteoblasts and their progeny (osterix promoted Cre) and vascular endothelial cells (vascular-endothelial-cadherin promoted Cre). Our objectives were to assess post-natal bone growth, structure and strength. We hypothesized that removal of BMP2 from osteogenic and vascular cells (separately) would result in smaller skeletons with inferior bone material properties. At 12 and 24 weeks of age the osteoblast knockout of BMP2 reduced body weight by 20%, but the vascular knockout had no effect. Analysis of bone in the tibia revealed reductions in cortical and cancellous bone size and volume in the osteoblast knockout, but not in the vascular endothelial knockout. Furthermore, forelimb strength testing revealed a 30% reduction in ultimate force at both 12 and 24 weeks in the osteoblast knockout of BMP2, but no change in the vascular endothelial knockout. Moreover, mechanical strength testing of femurs from osteoblast knockout mice demonstrated an increased Young's modulus (greater than 35%) but decreased post-yield displacement (greater than 50%) at both 12 and 24 weeks of age. In summary, the osteoblast knockout of BMP2 reduced bone size and altered mechanical properties at the whole-bone and material levels. Osteoblast-derived BMP2 has an important role in post-natal skeletal growth, structure and strength, while vascular endothelial-derived BMP2 does not.
Department of Orthopaedic Surgery, Musculoskeletal Research Center, Washington University in St. Louis, St. Louis, Missouri, United States of America; Department of Orthopaedic Surgery, Saint Louis University, St. Louis, Missouri, United States of America.
Sarah H
SH
McBride
Department of Orthopaedic Surgery, Musculoskeletal Research Center, Washington University in St. Louis, St. Louis, Missouri, United States of America.
Jennifer A
JA
McKenzie
Department of Earth and Planetary Sciences, Washington University in St. Louis, St. Louis, Missouri, United States of America.
Bronwyn S
BS
Bedrick
Department of Orthopaedic Surgery, Musculoskeletal Research Center, Washington University in St. Louis, St. Louis, Missouri, United States of America.
Paige
P
Kuhlmann
Department of Earth and Planetary Sciences, Washington University in St. Louis, St. Louis, Missouri, United States of America.
Jill D
JD
Pasteris
Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts, United States of America.
Vicki
V
Rosen
Department of Orthopaedic Surgery, Musculoskeletal Research Center, Washington University in St. Louis, St. Louis, Missouri, United States of America.
Matthew J
MJ
Silva
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001696:Biomechanical Phenomena; D001846:Bone Development / Q000235:genetics / Q000502:physiology*; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism*; D001842:Bone and Bones / Q000033:anatomy & histology* / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000378:metabolism*; D010011:Osteocytes / Q000378:metabolism*; D013059:Spectrum Analysis, Raman; D055114:X-Ray Microtomography
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2