Anti-BMP6 (aa 382-471) polyclonal antibody

The manufacture of biomaterial surfaces with desired physical and chemical properties that can directly induce osteogenic differentiation without the need for biochemical additives is an excellent strategy for controlling the behavior of mesenchymal stem cells (MSCs) in vivo. We studied the cellular and molecular reactions of MSCs to samples with a double-sided calcium phosphate (CaP) coating and an average roughness index (Ra) of 2.4-4.6 mu m. The study aimed to evaluate the effect of a three-dimensional matrix on the relative mRNA expression levels of genes associated with the differentiation and maturation of MSCs toward osteogenesis (RUNX2, BMP2, BMP6, BGLAP, and ALPL) under conditions of distant interaction in vitro. Correlations were revealed between the mRNA expression of some osteogenic and cytokine/chemokine genes and the secretion of cytokines and chemokines that may potentiate the differentiation of cells into osteoblasts, which indicates the formation of humoral components of the extracellular matrix and the creation of conditions supporting the establishment of hematopoietic niches.

Hereditary Hemochromatosis (HH) is a genetically heterogeneous disorder caused by mutations in at least five different genes (HFE, HJV, TFR2, SLC40A1, HAMP) involved in the production or activity of the liver hormone hepcidin, a key regulator of systemic iron homeostasis. Nevertheless, patients with an HH-like phenotype that remains completely/partially unexplained despite extensive sequencing of known genes are not infrequently seen at referral centers, suggesting a role of still unknown genetic factors. A compelling candidate is Bone Morphogenetic Protein 6 (BMP6), which acts as a major activator of the BMP-SMAD signaling pathway, ultimately leading to the upregulation of hepcidin gene transcription. A recent seminal study by French authors has described three heterozygous missense mutations in BMP6 associated with mild to moderate late onset iron overload (IO). Using an updated next-generation sequencing (NGS)-based genetic test in IO patients negative for the classical HFE p.Cys282Tyr mutation, we found three BMP6 heterozygous missense mutations in four patients from three different families. One mutation (p.Leu96Pro) has already been described and proven to be functional. The other two (p.Glu112Gln, p.Arg257His) were novel, and both were located in the pro-peptide domain known to be crucial for appropriate BMP6 processing and secretion. In silico modeling also showed results consistent with their pathogenetic role. The patients' clinical phenotypes were similar to that of other patients with BMP6-related IO recently described. Our results independently add further evidence to the role of BMP6 mutations as likely contributing factors to late-onset moderate IO unrelated to mutations in the established five HH genes.