An Investigative Study Into the Relationship of Bone Morphogenetic Protein Antagonist Expression and Osteocyte Density by Region and Quadrant

Abstract

The role of cytokines and cell behavior and viability with respect to bone remodeling and bone behavior is an exciting area of orthopedic research. The purpose of this study was to investigate the relationships between BMP antagonist expression and osteocyte density, lacunar densities and osteocyte viability in cortical bone. Samples of unloaded tibial bone obtained from six C57Bl/6 mice were immunohistochemically stained for gremlin and noggin expression and also underwent methyl green staining to determine osteocyte presence. Bone sections were divided into four quadrants (cranial, caudal, medial and lateral) and three regions (proximal, mid shaft and distal), followed by analysis across these quadrants and regions. The results showed matching regional differences in gremlin expression with regional variations in osteocyte density, lacunar density, and osteocyte viability. These variations were supported by positive correlations found via regression analysis. Regression analysis also showed marginal negative correlations between noggin expression and osteocyte density and osteocyte viability, supported by regional ANOVA results. Further research on loaded bone samples is needed if the relationship between these BMP antagonists and osteocyte densities are to be fully explained with respect to the bone remodeling process.

A Study of Osteocyte Apoptosis by Region and Quadrant in Murine Cortical Bone

“…Coincidentally, in Mosher's previous study, the midshaft region demonstrated higher gremlin expression than both the proximal and distal regions as well (Mosher 2010). This indicates some relationship between BMP antagonists and apoptotic osteocytes that is confirmed by the regression analysis.…”

“…No quadrantal differences were seen in the percentage of apoptotic osteoctyes, total lacunar density, viable osteocyte density, and percentage of viable osteocytes as well. Mosher's study showed similar results with no differences between quadrants with respect to viable osteocyte density, total lacunar density, percentage of viable osteocyte, and gremlin expression (Mosher 2010). This overall lack of variation among quadrants is not uncharacteristic of unloaded bone conditions.…”

“…He compared BMP antagonist expression levels with varying osteocyte densities. While no significant differences were shown between quadrants, significant regional differences were found between the BMP antagonist levels of gremlin and osteocyte densities indicating some sort of relationship and influence on bone remodeling (Mosher 2010).…”

“…The total lacunar density was compared to previous studies measuring osteocyte densities in mice to validate this study. A similar study looking at BMP antagonist expression levels and using some of the same mice as the current study produced an overall osteocyte density of 676 per mm in mice hindlimbs (Mosher 2010). When the effect of osteoprotegerin, a protein affecting the formation of osteoclasts was studied, densities of 750-800 per mm 2 were reported in mice tibial diaphysis using H and E staining (Bucay, Sarosi et al 1998).…”