Counteracting Osteoclastic Resorption and Development of Osteoporosis via Rebalancing Gut Microbiota and thus Metabolite TMAO by Traditional Decoction Medicine
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PROVIDER: PRJNA1251532 | ENA |
REPOSITORIES: ENA
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Project description:Osteoporosis represents a significant health challenge, particularly in postmenopausal women. While traditional medicine offers potential solutions, the mechanisms underlying their efficacy remain elusive. This study demonstrates the bone-protective properties of Guilu Erxian gel decoction (GEX), a traditional medicine prepared from tortoise plastron, antler, and herbs, by elucidating its impact on gut microbiota and associated metabolites. Using an ovariectomized mouse model of postmenopausal osteoporosis, we demonstrate that GEX consumption significantly reduces key osteoporotic markers, including low bone mineral density, compromised trabecular microstructure, and reduced biomechanical strength. GEX intake profoundly reshapes the gut microbiome, enriching beneficial bacteria crucial for fatty acid metabolism and mineral absorption. Gut microbiota transplantation from GEX-fed mice to ovariectomized recipients reversed probiotic bacterial abundance, particularly Bifidobacterium and Akkermansia. This intervention effectively alleviated ovariectomy-induced colon inflammation, trimethylamine N-oxide (TMAO) overproduction, and osteoporosis progression. Excessive TMAO promotes osteoclastogenic differentiation in macrophages in vitro. Using μCT imaging, biomechanical testing, histological staining, and 16S rRNA sequencing, we provide compelling evidence for the complex therapeutic effects of GEX, including mitigation of osteoclast overburden, reduction of marrow adiposis, suppression of RANKL overproduction, and preservation of colon goblet cell mucin. This study demonstrates the interplay between gut microbiota, its metabolite TMAO, and bone health, offering new insights into the mechanism of action of GEX. Our findings not only validate the bone-protective potential of this traditional medicine but also open new avenues for developing microbiome-based strategies to combat osteoporosis.
2025-08-16 | GSE294739 | GEO
Project description:Estrogen clearly prevents osteoporotic bone loss by attenuating bone resorption. The molecular basis of how this is accomplished, however, remains elusive. Here we report a critical role of osteoclastic ERa in mediating estrogen action on bone in females. We selectively ablated ERa in differentiated osteoclasts (ERa dOc/dOc). ERa dOc/dOc females, but not males, exhibited clear trabecular bone loss, similar to the osteoporotic bone phenotype in post-menopausal women. Recovery of bone loss by estrogen treatment of the ovariectomized ERa dOc/dOc females was ineffective in the trabecular areas of the long bones and lumbar vertebral bodies. Osteoclastic apoptosis, induced by estrogen, occurred simultaneously with up-regulation of Fas ligand (FasL) expression in intact trabecular bones of ERa +/+mice, but not in ERa dOc/dOc mice. ERa was also required for similar effects of estrogen and tamoxifen in cultured osteoclasts. These findings suggest that the osteoprotective actions of estrogen and SERMS are mediated at least in part through osteoclastic ERa in trabecular bone; and the life span of mature osteoclasts is regulated through activation of the Fas/FasL system. Keywords: Study about estrogen response of osteoclast-specific estrogen receptor alpha mice
2007-06-01 | GSE7798 | GEO
Project description:AnxA1 inhibits pathological bone resorption
| PRJNA759264 | ENA
Project description:Feline tooth transcriptome changes involvement in feline tooth resorption (TR)
| PRJEB24183 | ENA
Project description:Comparison of osteoclastic differentiation pathway from DCs with the canonical differentiation pathway from monocytes by transcriptomic profiling
2009-09-01 | E-MEXP-2019 | biostudies-arrayexpress
Project description:The importance of extrinsic regulation of hematopoietic stem cell activity is increasingly acknowledged. Here we report the generation of a new niche system, which supports expansion of mouse hematopoietic stem cells in vitro. Characterization of this niche revealed a transcriptional regulatory network including four critical factors, namely FOS, SPI1, KLF10 and TFEC. Interestingly, these factors are essential for osteoclastogenesis, thus revealing an osteoclastic network that supports hematopoietic stem cell self-renewal. Lentiviral vectors containing putative transcription factors regulating HSC expansion were transfected into GPE cells and gene expression values were compared to empty vector controls.
2013-12-31 | E-GEOD-39835 | biostudies-arrayexpress
Project description:The importance of extrinsic regulation of hematopoietic stem cell activity is increasingly acknowledged. Here we report the generation of a new niche system, which supports expansion of mouse hematopoietic stem cells in vitro. Characterization of this niche revealed a transcriptional regulatory network including four critical factors, namely FOS, SPI1, KLF10 and TFEC. Interestingly, these factors are essential for osteoclastogenesis, thus revealing an osteoclastic network that supports hematopoietic stem cell self-renewal.
2013-12-31 | GSE39835 | GEO
Project description:Septins are known to play key roles in supporting cytoskeletal stability, vesicular transport, endo-/exocytosis, stabilizing cellular membranes and forming diffusion barriers. Their function in mammalian cells is poorly investigated. The osteoclast offers an interesting tool to investigate septins because all cellular activities septins were reported to be involved in are critical for osteoclasts. However, the existence of septins in osteoclasts has not even been reported. Here we show that the SEPT9 gene and Septin 9 (SEPT9) protein are expressed and synthesized during differentiation of human osteoclasts. Pharmacological stabilization of septin filaments dose dependently inhibits bone resorption of human osteoclasts in vitro suggesting a role for septins in bone resorption. Attesting to this, conditional deletion of Sept9 in mice leads to elevated levels of trabecular bone and diminished femoral growth in vivo. Finally, systematic interrogation of the spatial organization of SEPT9 by confocal microscopy reveals that SEPT9 is closely associated to the structures known to be critical for osteoclast activity. We propose that septins in general and SEPT9 in particular play a previously unappreciated role in osteoclastic bone resorption.
| S-EPMC6115361 | biostudies-literature
Project description:Osteoclasts resorb bone via the ruffled border, whose complex folds are generated by secretory lysosome fusion with bone-apposed plasma membrane. Lysosomal fusion with the plasmalemma results in acidification of the resorptive microenvironment and release of CatK to digest the organic matrix of bone. The means by which secretory lysosomes are directed to fuse with the ruffled border are enigmatic. We show that proteins essential for autophagy, including Atg5, Atg7, Atg4B, and LC3, are important for generating the osteoclast ruffled border, the secretory function of osteoclasts, and bone resorption in vitro and in vivo. Further, Rab7, which is required for osteoclast function, localizes to the ruffled border in an Atg5-dependent manner. Thus, autophagy proteins participate in polarized secretion of lysosomal contents into the extracellular space by directing lysosomes to fuse with the plasma membrane. These findings are in keeping with a putative link between autophagy genes and human skeletal homeostasis.
| S-EPMC3244473 | biostudies-literature
Project description:BACKGROUND AND PURPOSE:Gallium (Ga) has been shown to be effective in the treatment of disorders associated with accelerated bone loss, including cancer-related hypercalcemia and Paget's disease. These clinical applications suggest that Ga could reduce bone resorption. However, few studies have studied the effects of Ga on osteoclastic resorption. Here, we have explored the effects of Ga on bone cells in vitro. EXPERIMENTAL APPROACH:In different osteoclastic models [osteoclasts isolated from long bones of neonatal rabbits (RBC), murine RAW 264.7 cells and human CD14-positive cells], we have performed resorption activity tests, staining for tartrate resistant acid phosphatase (TRAP), real-time polymerase chain reaction analysis, viability and apoptotic assays. We also evaluated the effect of Ga on osteoblasts in terms of proliferation, viability and activity by using an osteoblastic cell line (MC3T3-E1) and primary mouse osteoblasts. KEY RESULTS:Gallium dose-dependently (0-100 microM) inhibited the in vitro resorption activity of RBC and induced a significant decrease in the expression level of transcripts coding for osteoclastic markers in RAW 264.7 cells. Ga also dramatically reduced the formation of TRAP-positive multinucleated cells. Ga down-regulated in a dose-dependant manner the expression of the transcription factor NFATc1. However, Ga did not affect the viability or activity of primary and MC3T3-E1 osteoblasts. CONCLUSIONS AND IMPLICATIONS:Gallium exhibits a dose-dependent anti-osteoclastic effect by reducing in vitro osteoclastic resorption, differentiation and formation without negatively affecting osteoblasts. We provide evidence that this inhibitory mechanism involves down-regulation of NFATc1 expression, a master regulator of RANK-induced osteoclastic differentiation.
| S-EPMC2925491 | biostudies-literature