Cajaninstilbene acid inhibits osteoporosis through suppressing osteoclast formation and RANKL-induced signaling pathways.

Osteoporosis is a form of osteolytic disease caused by an imbalance in bone homeostasis, with reductions in osteoblast bone formation, and augmented osteoclast formation and resorption resulting in reduced bone mass. Cajaninstilbene acid (CSA) is a natural compound derived from pigeon pea leaves. CSA possesses beneficial properties as an anti-inflammatory, antibacterial, antihepatitis, and anticancer agent; however, its potential to modulate bone homeostasis and osteoporosis has not been studied. We observed that CSA has the ability to suppress RANKL-mediated osteoclastogenesis, osteoclast marker gene expression, and bone resorption in a dose-dependent manner. Mechanistically, it was revealed that CSA attenuates RANKL-activated NF-κB and nuclear factor of activated T-cell pathways and inhibited phosphorylation of key signaling mediators c-Fos, V-ATPase-d2, and ERK. Moreover, in osteoclasts, CSA blocked RANKL-induced ROS activity as well as calcium oscillations. We further evaluated the therapeutic effect of CSA in a preclinical mouse model and showed that in vivo treatment of ovariectomized C57BL/6 mice with CSA protects the mice from osteoporotic bone loss. Thus, this study demonstrates that osteolytic bone diseases can potentially be treated by CSA.

Up-regulation of urinary exosomal hsa-microRNA-200b-3p and hsa-microRNA-206 in patients of steroid-induced osteonecrosis of femoral head.

The aim of this study was to determine the value of microRNAs (miRNAs) in urinary exosomes in the diagnosis of steroid-induced osteonecrosis of femoral head (SONFH). RNA was extracted from urinary exosomes from 9 SONFH patients and 9 hip osteoarthritis (HOA) patients with age and gender matched and then miRNAs were analyzed by next generation sequencing. Intriguingly, 15 miRNAs including hsa-miR-200b-3p and hsa-miR-206 were significantly upregulated in exosomes from SONFH patients. Furthermore, qRT-PCR and area under curve (AUC) analysis of an independent cohort of 30 SONFH patients, 10 HOA patients and 10 healthy donors confirmed that hsa-miR-200b-3p and hsa-miR-206 were upregulated in SONFH samples which AUC values were 0.938 (95% CI: 0.828-1) and 0.926 (95% CI: 0.806-1) respectively. GO function, KEGG pathway, miRNAs-mRNAs network and protein-protein interaction (PPI) network were also constructed to analyze potentially pathological mechanisms. The enriched functions and pathways included Hippo, PI3K-Akt, TGF-ß and Wnt signaling pathways. The top five hub genes (MAPK1, EP300, RHOA, PIK3CA, and CBL) were selected from PPI network, which consisted of 180 nodes and 518 edges. Collectively, our results showed that hsa-miR-200b-3p and hsa-miR-206 in urinary exosomes might serve as non-invasive biomarkers for SONFH.

Functional Morphology and Defensive Behavior in a Social Aphid.

Social aphids produce different morphs, which are genetically identical but morphologically different. Each morph performs a different duty in its community. Social aphids usually produce morphologically distinct soldiers to protect their colonies. The social aphid Pseudoregma bambucicola produces sterile first instar soldiers with specialized body parts and unique defensive behaviors, such as hind leg waving. By using this species as a research model, this study tested the assumption that the functional morphological basis of defensive behaviors of soldiers is related to specialized body parts. Field observations and a comprehensive morphometric analysis were carried out for natural populations. The results showed significant differences in functional morphology between soldiers, first instar nymphs, and adults. Elongated hind legs in soldiers are an important functional morphological basis for the deimatic behavior of hind leg waving, while sclerotized front legs and head horns are related to the function of directly attacking natural enemies. The size variation of different body parts among different morphs also indicates a cost-benefit trade-off in the evolution of the social aphid species.