Dataset Information

Curculigoside Ameliorates Bone Loss by Influencing Mesenchymal Stem Cell Fate in Aging Mice.

ABSTRACT: Senile osteoporosis is characterized by increased bone loss and fat accumulation in marrow. Curculigoside (CCG) is the major bioactive component of Curculigo orchioides, which has been used as anti-osteoporosis therapy for elder patients since antiquity. We aimed to investigate the underlying mechanisms by which CCG regulated the bone-fat balance in marrow of aging mice. In our study, CCG treatment was identified to interfere with the stem cell lineage commitment both in vivo and in vitro. In vivo, CCG promoted the transcriptional co-activator with PDZ-binding motif (TAZ) expression to reverse age-related bone loss and marrow adiposity. In vitro, proper concentration of CCG upregulated TAZ expression to increase osteogenesis and decrease adipogenesis of bone marrow mesenchymal stem cells (BMSCs). This regulating effect was discounted by TAZ knockdown or the use of MEK-ERK pathway inhibitor, UO126. Above all, our study confirmed the rescuing effects of CCG on the differential shift from adipogenesis to osteogenesis of BMSCs in aging mice and provided a scientific basis for the clinical use of CCG in senile osteoporosis.

SUBMITTER: Wang N

PROVIDER: S-EPMC8678408 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Curculigoside Ameliorates Bone Loss by Influencing Mesenchymal Stem Cell Fate in Aging Mice.

Wang Na N Li Ziyi Z Li Shilun S Li Yukun Y Gao Liu L Bao Xiaoxue X Wang Ke K Liu Chang C Xue Peng P Liu Sijing S

Frontiers in cell and developmental biology 20211203

Senile osteoporosis is characterized by increased bone loss and fat accumulation in marrow. Curculigoside (CCG) is the major bioactive component of Curculigo orchioides, which has been used as anti-osteoporosis therapy for elder patients since antiquity. We aimed to investigate the underlying mechanisms by which CCG regulated the bone-fat balance in marrow of aging mice. In our study, CCG treatment was identified to interfere with the stem cell lineage commitment both <i>in vivo</i> and <i>in vi ...[more]

PMID: 34926455

Similar Datasets

Project description:Background: Hair follicles harbor a rich autologous stem cell pool and human hair follicle-derived mesenchymal stem cells (hHF-MSCs) have multi-lineage differentiation potential. Many sources of MSCs include hHF-MSCs have been attractive candidates for cell therapy, regenerative medicine and tissue engineering. The present study is to explore the effect of intravenous transplantation of hHF-MSCs on bone mass in osteoporotic mice and its mechanism, and provides prospects for clinical applications for the treatment of osteoporosis with hHF-MSCs. Methods: Physically pull out about 20 hairs with intact hair follicles from the occipital area of the scalp of healthy volunteers, and extract hair follicle-derived fibroblast-like cells. These cells were cultured and characterized in vitro. Intravenous injection of hHF-MSCs was performed on ovariectomy-induced and age-related osteoporotic SCID mice for osteoporosis treatment. The mice were sacrificed 7 weeks after the second injection and samples were collected. The long bones and L1 vertebrae were collected for micro-CT scan, histomorphometry and immunohistochemical analysis. Peripheral serum were collected for ELISA analysis and antibody array. Results: Hair follicle-derived fibroblast-like cells were defined as hHF-MSCs. Intravenous transplantation of hHF-MSCs can better restores trabecular bone mass in osteoporotic mice. The double calcein labeling assay, trap staining of bones and ELISA analysis in peripheral serum showed enhanced bone formation and weakened bone resorption after transplantation. Antibody array and immunohistochemical analysis showed that several cytokines including OPG, Wnt2b, Noggin, VCAM-1 and RANKL might be involved in this process. Conclusion: Human HF-MSCs transplantation can combat trabecular bone loss induced by menopause and aging in mice. And the above mechanism that hHF-MSCs transplantation inhibits bone resorption and promote bone formation is related to OPG, Wnt2b, VCAM-1, Noggin and RANKL.

Project description:Senile osteoporosis (OP) is often concomitant with decreased autophagic activity. OPTN (optineurin), a macroautophagy/autophagy (hereinafter referred to as autophagy) receptor, is found to play a pivotal role in selective autophagy, coupling autophagy with bone metabolism. However, its role in osteogenesis is still mysterious. Herein, we identified Optn as a critical molecule of cell fate decision for bone marrow mesenchymal stem cells (MSCs), whose expression decreased in aged mice. Aged mice revealed osteoporotic bone loss, elevated senescence of MSCs, decreased osteogenesis, and enhanced adipogenesis, as well as optn-/ - mice. Importantly, restoring Optn by transplanting wild-type MSCs to optn-/ - mice or infecting optn-/ - mice with Optn-containing lentivirus rescued bone loss. The introduction of a loss-of-function mutant of OptnK193R failed to reestablish a bone-fat balance. We further identified FABP3 (fatty acid binding protein 3, muscle and heart) as a novel selective autophagy substrate of OPTN. FABP3 promoted adipogenesis and inhibited osteogenesis of MSCs. Knockdown of FABP3 alleviated bone loss in optn-/ - mice and aged mice. Our study revealed that reduced OPTN expression during aging might lead to OP due to a lack of FABP3 degradation via selective autophagy. FABP3 accumulation impaired osteogenesis of MSCs, leading to the occurrence of OP. Thus, reactivating OPTN or inhibiting FABP3 would open a new avenue to treat senile OP.Abbreviations: ADIPOQ: adiponectin, C1Q and collagen domain containing; ALPL: alkaline phosphatase, liver/bone/kidney; BGLAP/OC/osteocalcin: bone gamma carboxyglutamate protein; BFR/BS: bone formation rate/bone surface; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CDKN1A/p21: cyclin-dependent kinase inhibitor 1A; CDKN2A/p16: cyclin dependent kinase inhibitor 2A; CDKN2B/p15: cyclin dependent kinase inhibitor 2B; CEBPA: CCAAT/enhancer binding protein (C/EBP), alpha; COL1A1: collagen, type I, alpha 1; Ct. BV/TV: cortical bone volume fraction; Ct. Th: cortical thickness; Es. Pm: endocortical perimeter; FABP4/Ap2: fatty acid binding protein 4, adipocyte; H2AX: H2A.X variant histone; HE: hematoxylin and eosin; MAP1LC3B: microtubule-associated protein 1 light chain 3 beta; MAR: mineral apposition rate; MSCs: bone marrow mesenchymal stem cells; NBR1: NBR1, autophagy cargo receptor; OP: osteoporosis; OPTN: optineurin; PDB: Paget disease of bone; PPARG: peroxisome proliferator activated receptor gamma; Ps. Pm: periosteal perimeter; qRT-PCR: quantitative real-time PCR; γH2AX: Phosphorylation of the Serine residue of H2AX; ROS: reactive oxygen species; RUNX2: runt related transcription factor 2; SA-GLB1: senescence-associated (SA)-GLB1 (galactosidase, beta 1); SP7/Osx/Osterix: Sp7 transcription factor 7; SQSTM1/p62: sequestosome 1; TAX1BP1: Tax1 (human T cell leukemia virus type I) binding protein 1; Tb. BV/TV: trabecular bone volume fraction; Tb. N: trabecular number; Tb. Sp: trabecular separation; Tb. Th: trabecular thickness; μCT: micro computed tomography.

Project description:IntroductionSecondary osteoporosis is common in systemic lupus erythematosus and leads to a reduction in quality of life due to fragility fractures, even in patients with improvement of the primary disorder. Systemic transplantation of mesenchymal stem cells could ameliorate bone loss and autoimmune disorders in a MRL/lpr mouse systemic lupus erythematosus model, but the detailed therapeutic mechanism of bone regeneration is not fully understood. In this study, we transplanted human bone marrow mesenchymal stem cells (BMMSCs) and stem cells from exfoliated deciduous teeth (SHED) into MRL/lpr mice and explored their therapeutic mechanisms in secondary osteoporotic disorders of the systemic lupus erythematosus model mice.MethodsThe effects of systemic human mesenchymal stem cell transplantation on bone loss of MRL/lpr mice were analyzed in vivo and ex vivo. After systemic human mesenchymal stem cell transplantation, recipient BMMSC functions of MRL/lpr mice were assessed for aspects of stemness, osteogenesis and osteoclastogenesis, and a series of co-culture experiments under osteogenic or osteoclastogenic inductions were performed to examine the efficacy of interleukin (IL)-17-impaired recipient BMMSCs in the bone marrow of MRL/lpr mice.ResultsSystemic transplantation of human BMMSCs and SHED recovered the reduction in bone density and structure in MRL/lpr mice. To explore the mechanism, we found that impaired recipient BMMSCs mediated the negative bone metabolic turnover by enhanced osteoclastogenesis and suppressed osteoblastogenesis in secondary osteoporosis of MRL/lpr mice. Moreover, IL-17-dependent hyperimmune conditions in the recipient bone marrow of MRL/lpr mice damaged recipient BMMSCs to suppress osteoblast capacity and accelerate osteoclast induction. To overcome the abnormal bone metabolism, systemic transplantation of human BMMSCs and SHED into MRL/lpr mice improved the functionally impaired recipient BMMSCs through IL-17 suppression in the recipient bone marrow and then maintained a regular positive bone metabolism via the balance of osteoblasts and osteoclasts.ConclusionsThese findings indicate that IL-17 and recipient BMMSCs might be a therapeutic target for secondary osteoporosis in systemic lupus erythematosus.

Dataset Information

Curculigoside Ameliorates Bone Loss by Influencing Mesenchymal Stem Cell Fate in Aging Mice.

Publications

Curculigoside Ameliorates Bone Loss by Influencing Mesenchymal Stem Cell Fate in Aging Mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets