Mesenchymal stem cells (MSCs) can be obtained from various tissues, and contain common features. However, an increasing number of reports have described variant properties dependent of cell sources. We examined (1) whether MSCs existed in several intraarticular tissues, (2) whether gene expression profiles in intraarticular tissue MSCs closely resembled each other, and (3) whether identified genes were specific to intraarticular tissue MSCs. Human synovium, meniscus, intraarticular ligament, muscle, adipose tissue, and bone marrow were harvested, and colony-forming cells were analyzed. All these cells showed multipotentiality and surface markers typical of MSCs. Gene profiles of intraarticular tissue MSCs and chondrocytes were closer to each other than those of extraarticular tissues MSCs. Among three characteristic genes specific for intraarticular tissue MSCs, we focused on proline arginine-rich end leucine-rich repeat protein (PRELP). Higher expression of PRELP was confirmed in chondrocytes and intraarticular tissue MSCs among three elderly and three young donors. Synovium MSCs stably expressed PRELP, contrarily, bone marrow MSCs increased PRELP expression during in vitro chondrogenesis. In conclusion, MSCs could be isolated from various intraarticular tissues including meniscus and ligament, gene expression profiles of intraarticular tissue MSCs closely resembled each other, and the higher expression of PRELP was characteristic of intraarticular tissue MSCs. ß

Colony stimulating factor 1 receptor (CSF1R) plays key roles in regulating development and function of the monocyte/macrophage lineage, including microglia and osteoclasts. Mono-allelic mutations of CSF1R are known to cause hereditary diffuse leukoencephalopathy with spheroids (HDLS), an adult-onset progressive neurodegenerative disorder. Here, we report seven affected individuals from three unrelated families who had bi-allelic CSF1R mutations. In addition to early-onset HDLS-like neurological disorders, they had brain malformations and skeletal dysplasia compatible to dysosteosclerosis (DOS) or Pyle disease. We identified five CSF1R mutations that were homozygous or compound heterozygous in these affected individuals. Two of them were deep intronic mutations resulting in abnormal inclusion of intron sequences in the mRNA. Compared with Csf1r-null mice, the skeletal and neural phenotypes of the affected individuals appeared milder and variable, suggesting that at least one of the mutations in each affected individual is hypomorphic. Our results characterized a unique human skeletal phenotype caused by CSF1R deficiency and implied that bi-allelic CSF1R mutations cause a spectrum of neurological and skeletal disorders, probably depending on the residual CSF1R function.

The Src family of tyrosine kinases play pivotal roles in regulating cellular functions characteristic of multicellular animals, including cell-cell interactions, cell-substrate adhesion, and cell migration. To investigate the functional alteration of Src kinases during evolution from a unicellular ancestor to multicellular animals, we characterized Src orthologs from the unicellular choanoflagellate Monosiga ovata and the primitive multicellular sponge Ephydatia fluviatilis. Here, we show that the src gene family and its C-terminal Src kinase (Csk)-mediated regulatory system already were established in the unicellular M. ovata and that unicellular Src has unique features relative to multicellular Src: It can be phosphorylated by Csk at the negative regulatory site but still exhibits substantial activity even in the phosphorylated form. Analyses of chimera molecules between M. ovata and E. fluviatilis Src orthologs reveal that structural alterations in the kinase domain are responsible for the unstable negative regulation of M. ovata Src. When expressed in vertebrate fibroblasts, M. ovata Src can induce cell transformation irrespective of the presence of Csk. These findings suggest that a structure of Src required for the stable Csk-mediated negative regulation still is immature in the unicellular M. ovata and that the development of stable negative regulation of Src may correlate with the evolution of multicellularity in animals.choanoflagellate ͉ Csk ͉ sponge

Drehmann sign is highly valuable for clinically evaluating the existence of FAI and for following up with observation or realignment to prevent early osteoarthritis.

Mesenchymal stem cells (MSCs) from a variety of mesenchymal tissue contain common features, but distinguishing properties dependent on their origin are emerging. We investigated morphological differences of human bone marrowMSCs, synovium-MSCs, and chondrocytes during in vitro chondrogenesis. Two hundred thousands cells were pelleted after centrifugation and cultured in chondrogenic media that contained BMP-2, TGF-b3, and dexamethasone. The pellets were analyzed histologically, immunohistologically, and electron microscopically. Before chondrogenic induction, trypsinized MSCs and chondrocytes looked similar. At day 1, the structure of the three masses was divided into two layers, and the most obvious differences in the three populations were observed in the deep zone. In bone marrow-MSCs, round cells accumulated without intercellular space, and the cells were mainly connected through intermediate junctions. In synovium-MSCs, elongated cells accumulated with small desmosomes and intercellular spaces could occasionally be seen. In chondrocytes, separated oval and polygonal cells connected only in a narrow spotty area through a small desmosome. At day 7, the structure of the three masses was divided into three layers, and the most obvious differences in the three populations were observed in the middle zone. In bone marrow-MSCs, the middle zone consisted of dense smaller cells and apoptotic cells. In synovium-MSCs, the middle zone consisted of dense arrayed wider cells and apoptotic cells. In chondrocytes, the middle zone was acellular without apoptotic cells. At day 21, the morphology of cells and extracellular space became similar in that each cell was located separately with abundant extracellular matrix. The superficial zone was still obvious in bone marrow-MSCs, but hardly seen both in synovium-MSCs and chondrocytes. In this study, we revealed morphological differences of bone marrow-MSCs, synovium-MSCs, and chondrocytes during in vitro chondrogenesis. The most obvious differences in the three populations were observed at day 1 in the deep zone.