morroniside and Osteoporosis

Morroniside (MOR) possesses antiosteoporosis (OP) effects, but its molecular target and relevant mechanisms remain unknown.. We investigated the effects of MOR on glucocorticoid-induced OP and osteoblastogenesis and its underlying mechanisms.. The effects of MOR (10-100 μM) on the proliferation and differentiation of MC3T3-E1 cells were studied. In cultured MC3T3. These findings demonstrated that MOR treatment promoted osteoblastogenesis and ameliorated glucocorticoid-induced OP by targeting SGLT2, which may provide therapeutic potential in managing glucocorticoid-induced OP.

Topics: Animals; Cell Differentiation; Cell Line; Glucocorticoids; Molecular Docking Simulation; Osteoblasts; Osteogenesis; Osteoporosis; Sodium; Sodium-Glucose Transporter 2; Zebrafish

Morroniside is known to improve osteoporosis by promoting osteoblastogenesis. The activation of PI3K/Akt/mTOR signaling is a significant mechanism in morroniside-promoted osteoblastogenesis. It is well known that protective autophagy is an important factor in osteoblastogenesis. However, the activation of mTOR signaling can inhibit autophagy. This study aimed to investigate the relationship between mTOR signaling and autophagy in morroniside-regulated osteoblastogenesis. In this study, we investigated the effect of morroniside on the autophagic activity (LC3 conversion rate, LC3-puncta formation, and autophagosome number) of differentiated osteoblast precursors (MC3T3-E1 cells). Then, we identified the roles of mTOR knockdown in morroniside-regulated alterations of autophagy and osteogenic parameters in MC3T3-E1 cells. Next, mTOR knockdown and overexpression were used to observe the roles of mTOR in morroniside-regulated alterations of autophagic molecules (Atg7, Atg13, and Beclin1). Subsequently, the additional value of the above autophagic molecules on morroniside-regulated osteogenic parameters in MC3T3-E1 cells was analyzed based on lentiviral transduction. Finally, combined with morroniside and TAT-Beclin1, the roles of Beclin1 upregulation in the

Topics: Animals; Apoptosis Regulatory Proteins; Autophagy; Beclin-1; Mice; Osteoporosis; Phosphatidylinositol 3-Kinases; TOR Serine-Threonine Kinases

Bone remodeling is a continuous process of bone synthesis and destruction that is regulated by osteoblasts and osteoclasts. Here, we investigated the anti-osteoporotic effects of morroniside in mouse preosteoblast MC3T3-E1 cells and mouse primary cultured osteoblasts and osteoclasts in vitro and ovariectomy (OVX)-induced mouse osteoporosis in vivo. Morroniside treatment enhanced alkaline phosphatase activity and positively stained cells via upregulation of osteoblastogenesis-associated genes in MC3T3-E1 cell lines and primary cultured osteoblasts. However, morroniside inhibited tartrate-resistant acid phosphatase activity and TRAP-stained multinucleated positive cells via downregulation of osteoclast-mediated genes in primary cultured monocytes. In the osteoporotic animal model, ovariectomized (OVX) mice were administered morroniside (2 or 10 mg/kg/day) for 12 weeks. Morroniside prevented OVX-induced bone mineral density (BMD) loss and reduced bone structural compartment loss in the micro-CT images. Taken together, morroniside promoted increased osteoblast differentiation and decreased osteoclast differentiation in cells, and consequently inhibited OVX-induced osteoporotic pathogenesis in mice. This study suggests that morroniside may be a potent therapeutic single compound for the prevention of osteoporosis.

Topics: Animals; Bone Density; Bone Density Conservation Agents; Bone Remodeling; Cell Differentiation; Cell Line; Cell Survival; Cornus; Disease Models, Animal; Female; Glycosides; Mice; Mice, Inbred ICR; Osteoblasts; Osteoclasts; Osteogenesis; Osteoporosis; Ovariectomy; Phytotherapy; Plant Extracts

High glucose (HG)-mediated bone marrow mesenchymal stem cell (BMSC) dysfunction plays a key role in impaired bone formation induced by type 1 diabetes mellitus (T1DM). Morroniside is an iridoid glycoside derived from the Chinese herb Cornus officinalis, and it has abundant biological activities associated with cell metabolism and tissue regeneration. However, the effects and underlying mechanisms of morroniside on HG-induced BMSC dysfunction remain poorly understood.. Alkaline phosphatase (ALP) staining, ALP activity and Alizarin Red staining were performed to assess the osteogenesis of BMSCs. Quantitative real-time PCR and Western blot (WB) were used to investigate the osteo-specific markers, receptor for advanced glycation end product (RAGE) signalling and glyoxalase-1 (Glo1). Additionally, a T1DM rat model was used to assess the protective effect of morroniside in vivo.. Morroniside treatment reverses the HG-impaired osteogenic differentiation of BMSCs in vitro. Morroniside suppressed advanced glycation end product (AGEs) formation and RAGE expression by triggering Glo1. Moreover, the enhanced osteogenesis due to morroniside treatment was partially blocked by the Glo1 inhibitor, BBGCP2. Furthermore, in vivo, morroniside attenuated bone loss and improved bone microarchitecture accompanied by Glo1 upregulation and RAGE downregulation.. These findings suggest that morroniside attenuates HG-mediated BMSC dysfunction partly through the inhibition of AGE-RAGE signalling and activation of Glo1 and may be a potential treatment for diabetic osteoporosis.

Topics: Animals; Cell Differentiation; Glycation End Products, Advanced; Glycosides; Mesenchymal Stem Cells; Osteogenesis; Osteoporosis; Rats, Sprague-Dawley; Receptor for Advanced Glycation End Products; Wound Healing