Nano crystals impact stem cell fate during bone formation
Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of Biofunctional Macromolecular Chemistry at the Institute for Macromolecular Chemistry and Professor of Cell Signalling Environments in the Cluster of Excellence BIOSS Centre for Biological Signalling Studies at the University of Freiburg led the study. The team published the results in the prestigious journal Proceedings of the National Academy of Sciences – USA.
Bone tissue is a nano-composite: The inorganic mineral phase so called hydroxyapatite confers the bone stability, and these calcium-containing nano crystals are dispersed in an organic framework consisting of the protein collagen. Although bone tissue rejuvenates itself throughout one’s life, inducing damaged bone to repair has proved challenging.
The destruction of unhealthy bone is a necessary step in the saga of new bone formation. During this destruction of bone, many biomolecules that are stored in the organic matrix are released and they play a role in the bone restoration process by coaxing mesenchymal stem cells (MSCs) that reside in the bone marrow – to actively form bone.
This step presents a crossroad of sorts in the process of bone regeneration in that, MSCs can become bone cells and deposit bone or become cartilage cells and deposit a cartilage matrix (the callus) which then is transformed into bone. How the accompanying degradation of the hydroxyapatite matrix affects this crossroad has remained a mystery of sorts.
Using a biomimetic bone-like mineral phase developed (doi: 10.1002/adma.201701629) in the laboratory of Shastri, the team of scientists have unraveled that the bone mineral phase is a key “decision maker” in bone formation. In the study post-doctoral associate Dr. Melika Sarem from the group of Shastri, in collaboration with the research group of Prof. Ivan Martin at the Department of Biomedicine (University Hospital Basel, University of Basel), have discovered that the mineral phase of bone can stimulate a receptor called extracellular calcium sensing receptor (CaSR), a protein that senses calcium outside the cells and is expressed by MSCs. Over stimulation of CaSR forces MSCs to directly form bone as opposed to via a cartilage step.
They further report that interfering with signaling via CaSR can completely shut down the formation of bone in vivo. However, in a twist to this molecular dance, they have found that stimulating parathyroid hormone-1 receptor (PTH1R), the key regulator of calcium ion homeostasis, can rescue MSCs from the clutches of CaSR and promote the formation of bone via a cartilage intermediate. “Our discovery offers new insights into how bone mineral phase can dictate new bone formation” says Prof. Shastri. The findings of our study have huge implication for designing novel implant surface for bone regeneration” adds Dr. Sarem.
In diseases such as osteoporosis, bone is degraded with very little renewal of the lost bone. “Our study places CaSR squarely at the middle of the bone regeneration paradigm and we can now say that it is a master regulator of bone formation and this might explain why osteoporotic patients have a hard time healing their fractures” says Shastri.
Melika Sarem, Miriam Heizmann, Andrea Barbero, Ivan Martin, and V. Prasad Shastri (2018): Hyperstimulation of CaSR in human MSCs by biomimetic apatite inhibits endochondral ossification via temporal down-regulation of PTH1R. In: PNAS. doi: 10.1073/pnas.1805159115
The image is false colored scanning electron micrograph, where mineral phase (biomimetic bone like hydroxyapatite) is denoted by green and the matrix deposited by mesenchymal stem cells is shown in purple.
Source: Melika Sarem, Vincent Ahmadi and V. Prasad Shastri
Prof. Dr. Prasad Shastri
Institute for Macromolecular Chemistry & BIOSS Centre for Biological Signalling Studies
University of Freiburg
Rudolf-Werner Dreier | idw - Informationsdienst Wissenschaft
Unique brain 'fingerprint' can predict drug effectiveness
11.07.2018 | McGill University
Direct conversion of non-neuronal cells into nerve cells
03.07.2018 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
16.07.2018 | Physics and Astronomy
16.07.2018 | Life Sciences
16.07.2018 | Earth Sciences