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Mechanical pain sensing, adipogenesis, and STING-dependent innate immunity seem three distinct biological processes without substantial relationships. Intriguingly, TMEM120A, a transmembrane protein, has been shown to detect mechanical pain stimuli as a mechanosensitive channel, contribute to adipocyte differentiation/function by regulating genome organization and promote STING trafficking to active cellular innate immune response. However, the role of TMEM120A as a mechanosensitive channel was challenged by recent studies which cannot reproduce data supporting its role in mechanosensing. Furthermore, the molecular mechanism by which TMEM120A contributes to adipocyte differentiation/function and promotes STING trafficking remains elusive. In this review, we discuss these multiple proposed functions of TMEM120A and hypothesize the molecular mechanism underlying TMEM120A's role in fatty acid metabolism and STING signaling.

During endochondral ossification of long bones, the proliferation and differentiation of chondrocytes cause them to be arranged into layered structures constituting the epiphyseal growth plate, where they secrete the cartilage matrix that is subsequently converted into trabecular bone. Ca

During endochondral ossification of long bones, the proliferation and differentiation of chondrocytes cause them to be arranged into layered structures constituting the epiphyseal growth plate, where they secrete the cartilage matrix that is subsequently converted into trabecular bone. Ca2+ signaling has been implicated in chondrogenesis in vitro. Through fluorometric imaging of bone slices from embryonic mice, we demonstrated that live growth plate chondrocytes generated small, cell-autonomous Ca2+ fluctuations that were associated with weak and intermittent Ca2+ influx. Several genes encoding Ca2+-permeable channels were expressed in growth plate chondrocytes, but only pharmacological inhibitors of transient receptor potential cation channel subfamily M member 7 (TRPM7) reduced the spontaneous Ca2+ fluctuations. The TRPM7-mediated Ca2+ influx was likely activated downstream of basal phospholipase C activity and was potentiated upon cell hyperpolarization induced by big-conductance Ca2+-dependent K+ channels. Bones from embryos in which Trpm7 was conditionally knocked out during ex vivo culture exhibited reduced outgrowth and displayed histological abnormalities accompanied by insufficient autophosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in the growth plate. The link between TRPM7-mediated Ca2+ fluctuations and CaMKII-dependent chondrogenesis was further supported by experiments with chondrocyte-specific Trpm7 knockout mice. Thus, growth plate chondrocytes generate spontaneous, TRPM7-mediated Ca2+ fluctuations that promote self-maturation and bone development.

The trimeric intracellular cation (TRIC) channels TRIC-A and TRIC-B localize predominantly to the endoplasmic reticulum (ER) and likely support Ca(2+) release from intracellular stores by mediating cationic flux to maintain electrical neutrality. Deletion and point mutations in TRIC-B occur in families with autosomal recessive osteogenesis imperfecta. Tric-b knockout mice develop neonatal respiratory failure and exhibit poor bone ossification. We investigated the cellular defect causing the bone phenotype. Bone histology indicated collagen matrix deposition was reduced in Tric-b knockout mice. Osteoblasts, the bone-depositing cells, from Tric-b knockout mice exhibited reduced Ca(2+) release from ER and increased ER Ca(2+) content, which was associated with ER swelling. These cells also had impaired collagen release without a decrease in collagen-encoding transcripts, consistent with a defect in trafficking of collagen through ER. In contrast, osteoclasts, the bone-degrading cells, from Tric-b knockout mice were similar to those from wild-type mice. Thus, TRIC-B function is essential to support the production and release of large amounts of collagen by osteoblasts, which is necessary for bone mineralization.

Background: The aim of the study was to provide a point of reference to study the Neospora caninum infections in China. Methods: Genome DNA was extracted from the brains of aborted fetuses and specific PCR was performed with N. caninum Nc5-targeted specific primers. Fetal bovine brain tissues were homogenized and continuously cultured in Vero cells with double antibodies. The medium was replaced at 2-d intervals and the state of cells was observed. Results: A 608 bp Nc5 gene band was detected by PCR amplification. After sequencing,the sequence of the sample shared 99.5% homology with GenBank(AF061249). Brain homogenates were continuously cultured in Vero cells for 34 d and N. caninum was found. The results of IFAT and Nc5 gene-based PCR detection were N. caninum-positive, and the parasite was tentatively named N. caninum China Yanbian strain. BABL/c mice were inoculated with the separated parasites and showed clinical symptoms of ataxia and limb paralysis after 12 d. Only 3 mice survived.The blood of dying mice and the hearts, livers, spleens, lungs, kidneys, andbrains of dead mice were collected aseptically. The Nc5 gene-based PCR showed that N. caninum may exist in brains, livers, and spleen. Based on immunohistochemical observations, we showed that N. caninum tachyzoites existed in the brains and livers. Conclusion: We have successfully isolated bovine-specific N. caninum strain from brain tissues of aborted cattle in the China Yanbian region. This isolated strain has a strong infectious ability towards BABL/c mice.