New mediators of osteoblast mineralization

What is it about?

The bone synthesis is mediated by osteoblast, that mature from bone resident precursors to specialized secretor cells. This cell differentiation means an increase in demand of protein folding, traffic, quality control and secretion from osteoblast. The quality control machinery and the its role during maturation and differentiation of osteoblast has been poorly studied. We were interested in determining how this mechanism, and particularly the protein HERPUD1 could be modulate this process. HERPUD1 expression is strongly upregulated by the unfolded protein response and cellular stress and has been involved in control of endoplasmic reticulum-associated degradation (ERAD) and autophagy and is a key component of the ERAD multiprotein complex, helping to stabilize the complex and preventing the accumulation of unfolded ER proteins through dislocation to the cytosol and degradation by the proteasome. Pre-osteoblastic cell line and rat primary osteoblast differentiation was evaluated by measuring calcium deposit levels, alkaline phosphatase activity, and genetic markers of differentiation and we found that ERAD and proteasomal degradation were activated and HERPUD1 expression increased as osteoblast differentiation progressed. The decrease of HERPUD1 blocked osteoblast mineralization and significantly reduced ALP activity and its overexpression activated the osteoblast differentiation program.

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Why is it important?

Our results are important because described promising new intervention targets to maintain bone physiology

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