Gap junctional communication is involved in differentiation of osteoclasts from bone marrow and peripheral blood monocytes

Abstract

Aims: The aim of the study was to compare the influence of gap junctional communication (GJC) in osteoclastogenesis from bone marrow (BM) and peripheral blood (PB) monocytes. These widely used sources differ in purity, since BM cultures contain a significant number of stromal cells. We studied whether stimulation of GJC in BM monocyte/stromal cell cultures differs from the effect in pure PB monocyte cultures. We compared the differentiation also in acidosis, which is a known inducer of bone resorption. Main methods: Human BM and PB monocytes were isolated from BM aspirates or whole blood samples. The cells were cultured on human bone slices with osteoclastogenic growth factors and a GJC modulator, antiarrhythmic peptide AAP10, at physiological and acidic pH. Key findings: Both BM and PB monocytes differentiated into osteoclasts. Acidosis increased resorption in both cultures but stimulated cell fusion only in BM cultures, which demonstrates the role of stromal cells in osteoclastogenesis. At physiological pH, AAP10 increased the number of multinuclear cells and bone resorption in both BM and PB cultures indicating that GJC is involved in differentiation in both of these osteoclastogenesis assays. Interestingly, in PB cultures at pH 6.5 the stimulation of GJC with AAP10 inhibited both osteoclastogenesis and bone resorption suggesting a different role of GJC in BM and PB monocytes at stressed environment. Significance: The study is conducted with primary human tissue samples and adds new knowledge on factors affecting osteoclastogenesis from different monocyte sources.

Keywords

• Cell biology
• Developmental biology
• Stem cell research