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JHC exPRESS: First Published March 3, 2008. doi:10.1369/jhc.2008.950394
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A more recent version of this article appeared on June 1, 2008.
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Expression and Synthesis of Bone Morphogenetic Proteins by Osteoclasts: A Possible Path to Anabolic Bone Remodeling

Rama Garimella 1, Sarah E. Tague 1, Jianghong Zhang 1, Frank Belibi 1, Niru Nahar 1, B.H. Sun 1, Karl Insogna 1, Jinxi Wang 1 and H. Clarke Anderson 1*

1 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, Kansas City, Missouri (JZ); and Yale University School of Medicine, New Haven, Connecticut (BHS,KI)

* To whom correspondence should be addressed. E-mail: handerso{at}kumc.edu .

Submitted on November 27, 2007
Accepted on 15 February 2008


  Abstract
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 BMPs in osteoclasts, generated from primary co-cultures 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.

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


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