A loss-of-function mutation in the Lrp5 gene in mice leads to a low bone mass disorder due to the inhibition of the canonical Wnt signaling pathway; however, the role of bone marrow microenvironment in mice with this mutation remains unclear. In this study, we evaluated proliferation and osteogenic potential of mouse osteoblasts using the MTT assay and Alizarin red staining. The levels of alkaline phosphatase, tartrate-resistant acid phosphatase, and adiponectin in culture supernatants were measured using the enzyme-linked immunosorbent assay. Osteoclast bone resorbing activity was evaluated by toluidine staining and the number and area of bone resorption pits were determined. We observed increased osteogenesis in osteoblasts co-cultured with the BM-derived myeloid cells compared to the osteoblasts cultured alone. Mice with global Lrp5 deletion had a relatively higher bone density compared to the mice carrying osteoblast/osteocyte-specific Lrp5 deletion. An increased frequency of M2 macrophages and reduced expression of inflammatory cytokines were detected in the myeloid cells derived from the bone marrow of mice with global Lrp5 deletion. Higher adipogenic potential and elevated levels of adiponectin in the global Lrp5 deletion mice contributed to the preferential M2 macrophage polarization. Here, we identified a novel systemic regulatory mechanism of bone formation and degradation in mice with global Lrp5 deletion. This mechanism depends on a crosstalk between the adipocytes and M2 macrophages in the bone marrow and is responsible for partly rescuing osteopenia developed as a result of decreased Wnt signaling.
Crosstalk between adipocytes and M2 macrophages compensates for osteopenic phenotype in the Lrp5-deficient mice