Abstract
Human transthyretin (TTR) is a homotetramer that transports thyroid hormones and retinol in the serum and cerebrospinal fluid. TTR is also an intracellular protein found in tissues such as those in the brain, eye and pancreas. TTR is a nutrition marker, reflecting the health of the organism, and TTR levels are linked to the normal and diseased states of the body. The switch from a protective to a pathological role is attributed to the destabilisation of the TTR structure, which leads to tetramer dissociation and amyloid formation. Native and destabilised TTR have been associated with osteoarthritis and bone density in humans. Moreover, TTR is present in eggshell mammillary cones; therefore, we verified the putative TTR engagement in the process of mineral formation. Using an in vitro assay, we found that TTR affected calcium carbonate crystal growth and morphology, producing asymmetric crystals with a complex nanocrystalline composition. The crystals possessed rounded edges and corners and irregular etch pits, suggesting the selective inhibition of crystal growth and/or dissolution imposed by TTR. The occurrence of many porosities, fibrillary inclusions and amorphous precipitates suggested that destabilisation of the TTR structure is an important factor involved in the mineralisation process. Crystals grown in the presence of TTR exhibited the characteristic features of crystals controlled by biomineralisation-active proteins, suggesting novel functions of TTR in the mineral formation process.