Transcriptome Analysis Reveals That Abeliophyllum distichum Nakai Extract Inhibits RANKL-Mediated Osteoclastogenensis Mainly through Suppressing Nfatc1 Expression

Abstract

Abeliophyllum distichum Nakai is known as a monotypic genus endemic to South Korea. Currently, several pharmacological studies have revealed that A. distichum extract exhibits diverse biological functions, including anti-cancer, anti-diabetic, anti-hypertensive, and anti-inflammatory activities. In this study, we present the anti-osteoporotic activity of A. distichum extract by inhibiting osteoclast formation. First, we show that the methanolic extract of the leaves of A. distichum, but not extracts of the branches or fruits, significantly inhibits receptor activator of the NF-κB ligand (RANKL)-induced osteoclast differentiation. Second, our transcriptome analysis revealed that the leaf extract (LE) blocks sets of RANKL-mediated osteoclast-related genes. Third, the LE attenuates the phosphorylation of extracellular signal-related kinase. Finally, treatment with the LE effectively prevents postmenopausal bone loss in ovariectomized mice and glucocorticoid-induced osteoporosis in zebrafish. Our findings show that the extract of A. distichum efficiently suppressed osteoclastogenesis by regulating osteoclast-related genes, thus offering a novel therapeutic strategy for osteoporosis.

TMBIM6 deficiency leads to bone loss by accelerating osteoclastogenesis

“…The region of interest (ROI) for trabecular bone was defined as the area located 1 mm from the growth plates, and 100 slices (2 mm) were reconstructed. The trabecular bone parameters were analyzed and calculated using the ROI tool in Analyze 12.0 software (AnalyzeDirect, Overland Park, KS, USA) [ 38 ].…”

“…mRNA-Seq reads were aligned to reference mouse genome (mm10 assembly) using TopHat. HOMER program was used to analyze RNA-seq data performed as described [ 38 , 47 ]. The cut-off parameters were set at fold change ≥1.5 and FDR <0.05 (Benjamin-Hochberg).…”

Fish Models of Induced Osteoporosis

“…It is clear from the previous paragraph that natural extracts contain promising osteoactive compounds that may be used to develop next-generation drugs to treat osteoporosis. Because they bring many technical advantages into the cumbersome screening process, e.g., they allow larger and quicker screening assays, teleost OP models, in particular the zebrafish GIOP model, have been favored as first line screening assays and several osteogenic fractions and compounds derived from plants and fungi have already been identified ( Niu et al, 2015 ; Lee K. et al, 2020 ). Holistic approaches coupling network pharmacology modulation and zebrafish GIOP model as a screening platform to test the efficacy of identified matrixes were also successfully implemented.…”

Parkin Inhibits RANKL-Induced Osteoclastogenesis and Ovariectomy-Induced Bone Loss

“…Bone homeostasis is maintained by balancing bone formation and bone resorption; the primary function of osteoclasts is bone resorption. Postmenopausal osteoporosis is characterized by increased osteoclast number and activity [ 3 ].…”