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Originally published as JHC exPRESS on March 3, 2008.
doi:10.1369/jhc.2008.950394
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Journal of Histochemistry and Cytochemistry
Volume 56 (6): 569-577, 2008
Copyright ©The Histochemical Society, Inc.

Expression and Synthesis of Bone Morphogenetic Proteins by Osteoclasts: A Possible Path to Anabolic Bone Remodeling

Rama Garimella, Sarah E. Tague, Jianghong Zhang, Frank Belibi, Niru Nahar, Ben Hua Sun, Karl Insogna, Jinxi Wang and H. Clarke Anderson

Departments of Pathology and Laboratory Medicine (RG,SET,FB,NN,HCA) and Orthopedic Surgery (JW), University of Kansas Medical Center, Kansas City, Kansas; University of Missouri, Kansas City, Missouri (JZ); and Yale University School of Medicine, New Haven, Connecticut (BHS,KI)

Correspondence to: H. Clarke Anderson, MD, University of Kansas Medical Center, Department of Pathology, Kansas City, KS 66160. E-mail: handerso{at}kumc.edu

Skeletal remodeling is a finely orchestrated process coupling bone formation to bone resorption. The dynamics of coupling is regulated by the microenvironment at the bone remodeling site, which in turn is influenced by the intercellular communication between cells like osteoclasts and osteoblasts. Understanding the dynamics of coupling is important in devising new therapeutic approaches to the treatment of skeletal diseases characterized by disturbances in the bone remodeling process. In this study, we report the localization of bone morphogenetic proteins (BMPs) in osteoclasts generated from primary cocultures of bone marrow cells from mouse femur and tibia with mouse calvarial osteoblasts, using immunocytochemistry and in situ hybridization. Positive staining was seen in osteoclasts for BMP-2, -4, -6, and -7. Real-time PCR was used to quantitatively confirm the expression of transcripts for BMP-2, BMP-4, and BMP-6 mRNA in murine osteoclasts. Finally, the presence of BMP-2, -4, -6, and-7 proteins was confirmed in osteoclast lysates by Western blotting. Overall, our data suggest a possible direct role for osteoclasts in promoting bone formation via expression and synthesis of BMPs, which then would play an important role in promoting the recruitment, proliferation, and differentiation of osteoblasts at bone resorption sites. (J Histochem Cytochem 56:569–577, 2008)

Key Words: bone morphogenetic proteins • skeletal remodeling • coupling • osteoclasts • osteoblasts


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