Biomechanical forces have been shown to significantly affect tissue development, morphogenesis, pathogenesis and healing, especially in orthopaedic tissues. Such biological processes are critically related to the differentiation of human mesenchymal stem cells (hMSCs). However, the mechanistic details regarding how mechanical forces direct MSC This article is protected by copyright. All rights reserved. were upregulated in response to the increased magnitudes of compressive strain, whereas osteogenic markers (COL1A1, SPARC, RUNX2) and calcium deposition had noticeable decreases by compressive loading in a magnitude-dependent manner. Dynamic mechanical analysis showed enhanced viscoelastic modulus with respect to the increased dynamic strain peaking at 15%, which coincides with the maximal GAG synthesis. Furthermore, polarization-sensitive optical coherence tomography (PS-OCT) revealed that mechanical loading enhanced the alignment of extracellular matrix to the greatest level by 15% strain as well. Overall, we show that the degree of differentiation of hMSCs towards osteogenic or chondrogenic lineage is inversely related, and it depends on the magnitude of dynamic compressive strain. These results demonstrate that multi-phenotypic differentiation of hMSCs can be controlled by varying the strain regimens, providing a novel strategy to modulate differentiation specification and tissue morphogenesis.

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The reaction of a thiol with an isocyanide proceeds in two directions. In the first reaction (course a), the carbon atom of isocyanide with lone-pair electrons is inserted into the sulfur-hydrogen bond of thiol to produce thioformimidate (I). In the second reaction (course b), isothio-cyanate (II) and the alkane (III) from the alkyl group of thiol are formed. The proportion of the participation of two reactions depends upon the alkyl group of thiol and upon the reaction conditions including whether or not a catalyst is employed. Primary thiol prefers course a to course b, whereas tertiary thiol prefers course b. In the reactions at 15°C, the Group IB and IIB metal compounds, e. g., copper compounds, catalyzed the course a reaction preferably. At higher temperatures, e. g. at 100°C, thiol reacts with isocyanide quite rapidly, even in the absence of a catalyst. However, the catalyst effect favoring course a is seen even in the high-temperature reactions. The mechanism of the reaction, especially course b, has been discussed. Syn-anti structures of thioformimidate were also studied by NMR.

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