Effect of BMP-2 Protein on the Count and Osteogenic Properties of Multipotent Stromal Cells and Expression of Cytokine Genes in Primary Cultures of Bone Marrow and Spleen Cells from CBA Mice Immunized with Bacterial Antigens

Abstract

We studied the effect of BMP-2 added to the culture medium on osteogenic and proliferative properties of multipotent stromal cells (MSC) and on the expression of cytokine genes induced by immunization of experimental animals with bacterial antigens. It is shown that the presence of BMP-2 in the culture medium stimulates proliferation of bone marrow MSC and especially spleen MSC (which was seen from enlargement of MSC colonies); improves the efficiency of MSC cloning; increases osteogenic activity of mouse bone marrow MSC; induces osteogenic differentiation of splenic MSC (osteogenesis is normally not observed in the spleen); reduces the number of macrophages in cultures; inhibits synthesis of mRNA for proinflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α) that typically occurs in cultures of the bone marrow and spleen from animals immunized with S. typhimurium or group A streptococcus antigens. Bearing in mind that proinflammatory cytokines negatively affect osteogenic activity of the bone marrow, we can hypothesize that BMP-2 not only stimulates osteogenesis, but also provides optimal conditions for its realization by suppressing the expression of genes encoding these cytokines.

IL-1β-mediated TGFβ/SMAD signaling pathway inactivation impairedex vivoosteogenic activity of human bone marrow-derived stromal cells

“…It is well known that inflammatory cytokines play an essential role as negative modulators of osteogenesis and bone formation [40]. Numerous studies have demonstrated the inhibitory impact of IL-1β on MSC differentiation into osteoblasts and migration and down-regulation of osteoblastic-related gene expression [38,[41][42][43]. IL1β, a pleiotropic cytokine that mediates inflammation and the innate immune system, enhances bone resorption by stimulating osteoclast activation by inducing RANKL expression due to its mediating action by TNF-α [41].…”

Bone Morphogenetic Protein‐2 and Vascular Endothelial Growth Factor in Bone Tissue Regeneration: New Insight and Perspectives

“…A number of key molecules that regulate the complex bone regenerative physiological process have been identified and are already in clinical use for enhancing bone repair. Of these molecules, BMP‐2 has been the most extensively studied regarding induction of new bone formation in ectopic and orthotopic sites, including where there are critical size defects (CSDs). BMP‐2 has been found to be a promising alternative to autografts for non‐union of bone defects, open tibial fractures, spinal fusion and accelerated fracture healing.…”