Adiponectin inhibits osteoclastogenesis and bone resorption via APPL1-mediated suppression of Akt1.

Adiponectin is an adipokine playing an important role in regulating energy homeostasis and insulin sensitivity. However, the effect of adiponectin on bone metabolism shows contradictory results according to different research studies. In this study femurs were isolated from genetically double-labeled mBSP9.0Luc/ß-ACT-EGFP transgenic mice and were transplanted into adiponectin knock-out mice or wild type mice to investigate the effect of temporary exposure to adiponectin deficiency on bone growth and metabolism. We found that the growth of bone explants in adiponectin knock-out mice was significantly retarded. Histological analysis, microcomputed tomography analysis, and tartrate-resistant acid phosphatase staining revealed reduced trabecular bone volume, decreased cortical bone, and increased osteoclast number in bone explants in adiponectin knock-out mice. We then found that adiponectin inhibits RANKL-induced osteoclastogenesis from RAW264.7 cells and down-regulates RANKL-enhanced expressions of osteoclastogenic regulators including NFAT2, TRAF6, cathepsin K, and tartrate-resistant acid phosphatase. Adiponectin also increases osteoclast apoptosis and decreases survival/proliferation of osteoclast precursor cells. Using siRNA specifically targeting APPL1, the first identified adaptor protein of adiponectin signaling, we found that the inhibitory effect of adiponectin on osteoclasts was induced by APPL1-mediated down-regulation of Akt1 activity. In addition, overexpression of Akt1 successfully reversed adiponectin-induced inhibition in RANKL-stimulated osteoclast differentiation. In conclusion, adiponectin is important in maintaining the balance of energy metabolism, inflammatory responses, and bone formation.

Light-dependent and light-independent protochlorophyllide oxidoreductases in the chromatically adapting cyanobacterium Fremyella diplosiphon UTEX 481.

The cyanobacterium Fremyella diplosiphon can alternate its light-harvesting pigments, a process called comple-mentary chromatic adaptation (CCA), allowing it to photosynthesize in green light (GL) and in fluctuating light conditions. Nevertheless, F. diplosiphon requires chlorophylls for photosynthesis under all light conditions. Two alternative enzymes catalyze the penultimate step of chlorophyll synthesis, light-dependent protochlorophyllide oxidoreductase (LPOR) and dark-operative protochlo-rophyllide oxidoreductase (DPOR). DPOR enzymatic activity is light independent, while LPOR requires light. Therefore, we hypothesize that F. diplosiphon up-regulates DPOR gene expression in GL, so that DPOR is more abundant when LPOR is less functional. We cloned the genes encoding the three subunits of DPOR, chlL, chlN and chlB, and the LPOR gene, por, to determine the abundance of the transcripts under red light (RL), GL and dark conditions. We found that F. diplosiphon chlL and chlN genes are transcribed as parts of a single operon, a gene structure that is conserved within cyanobacteria. Tran-scripts levels of all DPOR genes are up-regulated approximately 2-fold in GL relative to levels in RL, whereas LPOR transcript levels are reduced in GL. Moreover, mutations in CCA regulators, RcaE and CpeR, modify DPOR and LPOR transcript levels under specific light conditions. Finally, both DPOR and LPOR transcripts are down-regulated 2- to 5-fold in the dark. These results provide the first evidence that light quality and CCA affect the genetic regulation of chlorophyll biosynthesis in freshwater cyanobacteria, ecologically important photosynthetic organisms.