Page 16 - Physico-Chemical Niche Conditions for Bone Cells

General introduction
connected to molecular complexes embedded in the nuclear envelope. Therefore, physical forces can be transmitted from the matrix environment into the nucleus [45]. Physical forces might also be transmitted to the nucleus via the primary cilium and microtubules. The primary cilium is a microtubule-based structure, which is crucial in physico-chemical-sensing in different cell types [46]. Microtubules are formed by the polymerization of a dimer of a and b tubulin into protofilaments [47]. The structure and network of microtubules, similar to that of actin, is highly dynamic; microtubule dynamics are regulated by posttranslational modifications (e.g. phosphorylation, acetylation, and detyrosination) and microtubule-associated proteins, which influence the homeostasis between microtubule growth and disassembly, as well as association with other cytoskeleton filaments [47]. The cytoskeleton filaments connect to the nuclear membrane via linker of nucleoskeleton and cytoskeleton complexes which are in the nuclear envelope and consist of nesprins (in the outer nuclear membrane) and SUN (Sad1p, UNC-84) proteins (in the inner nuclear membrane) [48]. There are 4 nesprin members, i.e. nesprin 1 to 4, which connect the nucleus to different cytoskeletal filaments [48]. Nesprin 1 and nesprin 2 directly connect to actin filaments [48]. Nesprin 3 is the only nesprin member to link intermediate filaments [48]. Nesprin 4 indirectly connects with microtubules via kinesin-1, whereas SUN proteins connect to the nuclear lamina, forming a bridge of nesprin and SUN protein between the cytoplasm and the nucleus [48]. Changes in nesprin expression might alter the shape of cell body and nucleus, leading to changes of cell function, e.g. differentiation. Therefore, it is also important to understand the mechanism of the cytoskeleton and some molecules in the processes of mechanosensing and mechanotransduction, which might help us to develop novel therapeutic treatment for bone diseases.
14