Osteoclasts are multinucleated cells that resorb bones, and are derived from hematopoietic cells of the monocyte/macrophage lineage. The receptor activator of NF-κB ligand (RANKL, also called ODF/TRANCE/OPGL) stimulates both osteoclast differentiation from osteoclast progenitors and activation of mature osteoclasts. To identify genes responsible for osteoclast differentiation, we used a molecular indexing technique. Here, we report a clone of one of these genes whose transcription is induced by soluble RANKL (sRANKL) in both the RAW264.7 cells of the mouse macrophage cell line and the mouse primary bone marrow cells. The predicted protein was found to be a mouse homologue of Jun dimerization protein 2 (JDP2), a member of the AP-1 family of transcription factors, containing a basic region-leucine zipper motif. Transient transfection experiments revealed that overexpression of JDP2 leads to activation of both tartrate-resistant acid phosphatase (TRAP) and cathepsin K gene promoters in RAW264.7 cells. Infection of mouse primary bone marrow cells with retroviruses expressing JDP2-facilitated sRANKL-mediated formation of TRAP-positive multinuclear osteoclasts. Importantly, antisense oligonucleotide to JDP2 strongly suppressed sRANKL-induced osteoclast formation of RAW264.7 cells. Our findings suggest that JDP2 may play an important role in the RANK-mediated signal transduction system, especially in osteoclast differentiation.

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Mesenchymal stem cells (MSCs) have therapeutic potential in various diseases, including myocardial infarction. Recently, the importance of the therapeutic effects of secreted factors from MSCs is increasing, but their identification has not progressed. In this study, we uncover the secreted protein profiles of MSCs derived from bone marrow, adipose tissue and dental pulp. Shotgun proteome analysis of conditioned MSC media by mass spectrometry identified 1533 proteins totally and 124 secreted proteins commonly produced among all three MSCs. The commonly secreted factors include already well-known factors whose functions are linked to MSCs' biological effects, such as CTGF, SERPINE1, TGFB1, DKK3 and MYDGF, and also include newly identified factors whose roles are not well investigated, for example AIMP1, CLEC11A, GAS6, HDGF, INHBA, and PCSK5. Computational biological pathway analysis revealed that these common factors strongly relate to tissue regeneration pathways such as angiogenesis, migration, and inflammatory response. Further analysis showed enrichment of ossification, sprouting, and organ survival factors, suggesting connection to the functions closely related to MSCs' therapeutic effects. This list of commonly secreted proteins could provide a reliable resource of biological factors which explain various effects of MSCs and would be useful for identifying new therapeutic factors produced from MSCs.

Our findings demonstrate that upregulated expression of DIO2 in OA patient cartilage might be responsible for OA pathogenesis by enhancing the chondrocyte hypertrophy and inflammatory response.

Alzheimer's amyloid precursor protein (APP) is a transmembrane protein containing three phosphorylation sites in its cytoplasmic domain. In the present study, we isolated cDNA of APP from electric ray electric lobe (elAPP). This APP (elAPP699) consists of 699 amino acids, contains the beta-amyloid domain and has 80.7% similarity with the human APP695 isoform. The cytoplasmic domain, including three phosphorylation sites, was completely conserved. In the nerve terminals of the cholinergic neuron from the electric ray electric organ, we found elAPP699 existed exclusively in the mature form. We found the phosphorylated form of mature elAPP699 in the nerve terminal as well as in cell body. Immature elAPP699 was not subject to phosphorylation. Our findings indicate that, in neurons, the phosphorylation of APP occurs after maturation.