Germline RBBP6 mutations in familial myeloproliferative neoplasm

Letter to the Edito

Germline RBBP6 mutations in familial myeloproliferative neoplasms

We have identified germline RBBP6 mutations in ∼5% of familial MPN cases (3/67) and in ∼0.6% of sporadic cases (3/490) where family history is unknown. The low penetrance present in MPN pedigrees suggests that the disease is triggered by some stochastic factors, perhaps the acquisition of somatic mutations. In addition, common germline predisposition factors, such as JAK2 GGCC haplotype and TERT rs2736100 SNP, seem to have an additive effect on the MPN risk in RBBP6 mutation carriers

Current views on calcium phosphate osteogenicity and the translation into effective bone regeneration strategies.

Calcium phosphate (CaP) has traditionally been used for the repair of bone defects because of its strong resemblance to the inorganic phase of bone matrix. Nowadays, a variety of natural or synthetic CaP-based biomaterials are produced and have been extensively used for dental and orthopaedic applications. This is justified by their biocompatibility, osteoconductivity and osteoinductivity (i.e. the intrinsic material property that initiates de novo bone formation), which are attributed to the chemical composition, surface topography, macro/microporosity and the dissolution kinetics. However, the exact molecular mechanism of action is unknown. This review paper first summarizes the most important aspects of bone biology in relation to CaP and the mechanisms of bone matrix mineralization. This is followed by the research findings on the effects of calcium (Ca(2)(+)) and phosphate (PO(4)(3)(-)) ions on the migration, proliferation and differentiation of osteoblasts during in vivo bone formation and in vitro culture conditions. Further, the rationale of using CaP for bone regeneration is explained, focusing thereby specifically on the material's osteoinductive properties. Examples of different material forms and production techniques are given, with the emphasis on the state-of-the art in fine-tuning the physicochemical properties of CaP-based biomaterials for improved bone induction and the use of CaP as a delivery system for bone morphogenetic proteins. The use of computational models to simulate the CaP-driven osteogenesis is introduced as part of a bone tissue engineering strategy in order to facilitate the understanding of cell-material interactions and to gain further insight into the design and optimization of CaP-based bone reparative units. Finally, limitations and possible solutions related to current experimental and computational techniques are discussed