scholarly journals Effects of Processed Polygonum multiflorum with KIOM Patent on Bone Remodeling-Related Protein Expression in Human Osteoblast-Like SaOS-2 Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-6 ◽  
Author(s):  
Dae Uk Kim ◽  
Jae Yoon Chung ◽  
Seong Chul Jin ◽  
Mi Hye Kim ◽  
Richard Komakech ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Remodeling ◽  
Bone Diseases ◽  
Oriental Medicine ◽  
Human Osteoblast ◽  
Related Protein ◽  
Polygonum Multiflorum ◽  
Black Bean ◽  
Related Proteins

This present study evaluated the effects of processed P. multiflorum on osteogenesis using Sarcoma osteogenic (SaOS-2) cell lines and osteoclastogenesis of bone marrow-derived macrophage cells (BMM) and to elucidate differences in effect on the expression of bone-related proteins between commercially sold P. multiflorum and patented, in vitro-propagated Korea Institute of Oriental Medicine (KIOM) P. multiflorum. Raw P. multiflorum and P. multiflorum that were stir-baked and steamed in black bean juice were compared, and western blotting analysis was performed to investigate the expression of bone remodeling-related proteins in SaOS-2 cells. In the cells treated with P. multiflorum steamed in black bean juice, the expression of RANKL was decreased, whereas that of osteoprotegerin, alkaline phosphatase, Runx2, and osterix was increased. Owing to these results, we conclude that processed P. multiflorum can be used as an alternative treatment for bone diseases such as osteoporosis, osteopenia, periodontitis, and Paget’s disease.

Osteocytes Support Hematopoiesis by Altering the Bone Marrow Microenvironment Through Gsα Signaling

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 219-219
Author(s):  
Daniela S. Krause ◽  
Keertik Fulzele ◽  
Kevin Barry ◽  
Sutada Lotinun ◽  
Roland Baron ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Remodeling ◽  
Conflicts Of Interest ◽  
Bone Matrix ◽  
Myeloid Cells ◽  
Hematopoietic Stem ◽  
Inflammatory Protein ◽  
G Protein Coupled

Abstract Abstract 219 Osteocytes, the most abundant and long living cells of bone embedded in the bone matrix, coordinate bone remodeling by regulating osteoblast and osteoclast activity, at least in part, via G-protein coupled receptor signaling. Osteoblasts and osteoclasts control hematopoiesis primarily by influencing self-renewal, differentiation, and mobilization of hematopoietic stem cells in their endosteal bone niche. A role for osteocytes in hematopoiesis has previously not been demonstrated. We engineered mice lacking Gsα in osteocytes (DMP1-GsαKO) using the Cre-loxP recombination technique. Consistent with the previously established role of osteocytes in regulation of bone remodeling, DMP1-GsαKO mice showed severe osteopenia and a decrease in cortical thickness. The osteopenia in the KO mice was due to a dramatic decrease in osteoblast numbers whereas the number and activity of osteoclasts was unaffected. In addition, DMP1-GsαKO mice displayed hematopoietic abnormalities that resembled a myeloproliferative syndrome (MPS) characterized by leukocytosis and neutrophilia. Myeloid cells were increased in the peripheral blood, bone marrow (BM), and spleen in DMP1-GsαKO mice compared to controls (p<0.01 in blood, BM and spleen, N≥6) as assessed by CBC and immunophenotypical flow cytometry analysis. Lineage- negative c-kit-positive and Sca-1+ (LKS) cells and LKS CD150-positive CD48-negative (LKS SLAM) cells were significantly increased in DMP1-GsαKO spleen compared to controls whereas there was no change in the bone marrow suggesting mobilization from the bone marrow in mutant mice. Surprisingly, the number of colonies formed in in-vitro methylcellulose assays from BM cells from DMP1-GsαKO mice were not changed indicating the requirement of the bone microenvironment to induce MPS. Co-culture of osteocyte-enriched bone explants from DMP1-GsαKO mice with control BM cells significantly increased the number of colonies compared to control explants. Transplantation of BM from control to DMP1-GsαKO mice rapidly recapitulated the MPS whereas converse transplantation completely normalized the hematopoietic abnormality. Protein expression of CXCL2 (macrophage inflammatory protein 2 alpha; MIP2-alpha), a chemotactic cytokine known to mobilize hematopoietic stem and myeloid cells, was markedly increased in Gsa deficient osteocytes as assessed by immunohistochemistry. Furthermore, CXCL2 secretion in conditioned media from osteocyte explants cultures was also increased 3-fold in Gsa deficient osteocytes as compared to controls. In summary, our results represent the first evidence for osteocyte-mediated regulation of hematopoiesis via Gsα-signaling-induced alteration of the BM microenvironment, possibly through CXCL2 signaling. Disclosures: No relevant conflicts of interest to declare.

Abstract 4: Deletion of Macrophage Low-density Lipoprotein Receptor-related Protein 1 (LRP1) Accelerates Atherosclerosis Regression by Increasing CCR7-dependent Egress of Plaque Macrophages

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Paul Mueller ◽  
Lin Zhu ◽  
Illaria Giunzioni ◽  
Hagai Tavori ◽  
John M Stafford ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Density Lipoprotein ◽  
Chow Diet ◽  
Related Protein ◽  
M1 Macrophages ◽  
M1 Macrophage ◽  
Anti Inflammatory ◽  
M2 Phenotype

We previously showed that mice lacking macrophage LDL receptor-related protein 1 (LRP1) undergo accelerated lesion formation due to increased apoptosis, decreased efferocytosis, and enhanced macrophage transformation into the inflammatory M1 phenotype. In vitro, LRP1-deficient macrophages (MΦLRP1 -/- ) show enhanced plasticity with exaggerated polarization towards either the inflammatory M1- or the anti-inflammatory M2-phenotype depending on the stimulant (LPS or IL-4, respectively). During atherosclerosis regression, the M2:M1 macrophage ratio increases as lesion M1 macrophages egress and inflammation resolves. Thus, we hypothesize that atherosclerosis regression is accelerated in MΦLRP1 -/- mice via enhanced macrophage M2 polarization and CCR7-dependent M1 macrophage egress. ApoE-/- mice on high fat diet for 12 weeks were reconstituted with bone marrow from wildtype (WT) or MΦLRP1 -/- mice and then placed on chow diet for 8 weeks. In this model, apoE is reintroduced into circulation to correct the hyperlipidemia and induce regression of atherosclerotic lesions. A cohort of apoE -/- mice reconstituted with apoE -/- bone marrow served as baseline controls. Lesions in both WT and MΦLRP1 -/- mice regressed relative to controls (11% and 22%, respectively; p<0.05), but MΦLRP1 -/- lesions were 13% smaller than those of WT mice (p<0.05). LRP1 deletion increased M2 transformation of macrophages and a higher M2:M1 macrophage ratio (p<0.01) in the plaque. MΦLRP1 -/- lesions contained 36% fewer M1 macrophages compared to WT (p<0.01). In vivo studies of reverse cholesterol transport (RCT) revealed that MΦLRP1 -/- have a 1.4-fold higher RCT compared to WT mice (p<0.01). MΦLRP1 -/- lesions contained 2.5-fold more CCR7 + macrophages relative to WT lesions (p<0.01), and in our in vivo egress assay 4.6-fold more CCR7 + macrophages were found in mediastinal lymph nodes. In vitro , M1-differentiated MΦLRP1 -/- macrophages expressed 1.6-fold higher Ccr7 mRNA compared to WT controls (p<0.01). Thus, the absence of macrophage LRP1 accelerates atherosclerosis regression due to enhanced transformation of macrophages into an anti-inflammatory M2 phenotype, increased cholesterol efflux, and increased CCR7-driven egress of M1 macrophages from lesions.

The Effect of Polygonum Multiflorum Extracts on Hematopoiesis and Platelet Production.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2159-2159
Author(s):  
Mo Yang ◽  
Wei Zhe Huang ◽  
Nga Hin Pong ◽  
Ai Guo Liu Liu ◽  
Chi Kong Li ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Monoamine Oxidase ◽  
Stromal Cells ◽  
Blood Cells ◽  
Bone Marrow Stromal Cells ◽  
Marrow Stromal Cells ◽  
Polygonum Multiflorum ◽  
Platelet Production ◽  
Vitro Effect

Abstract To date, there is no ideal treatment for thrombocytopenia. We have proposed a possible mechanism of serotonin (5-HT) on megakaryocyte (MK) differentiation and platelet formation (Yang et al, Blood, 2003 suppl). The root of polygonum multiflorum thunb (Heshouwu) is an important ingredient of many commonly used prescriptions in Chinese medicine for promoting blood production. Polygonum multiflorum extracts (PME) also inhibit monoamine oxidase (MAO) and increase the level of 5-HT. Therefore, we hypothesize that polygonum multiflorum may have a promoting effect on thrombopoiesis via inhibition of monoamine oxidase (MAO) to increase 5-HT levels. The objective of this study was to investigate the hematopoietic role of PME in irradiated mice. PME (125 mg/kg/day) and TPO (12.5 ug/kg/day) were given by intra-peritoneal injection daily for 21 days starting from the day after irradiation (4 Gy). Peripheral blood platelets, white blood cells (WBC), and red blood cells (RBC) were analyzed from PME, TPO, and vehicle control groups on day 0, 7, 14 and 21. On day 21, the mice were sacrificed and bone marrow cells were harvested for CFU-MK, CFU-GM, BFU-E, CFU-GEMM and CFU-F (fibroblastoid) assays (n=8). We also investigated the in vitro effect of PME on CFU-F formation. Our results showed that PME enhanced the recovery of platelets, WBC, and RBC counts. Moreover, PME also promoted CFU-MK (30 ± 8 vs 15 ± 3 colonies/2 x 105 cells, p<0.01), CFU-GM (38 ± 7 vs 28 ± 7 colonies/2 x 105 cells, p<0.05), BFU-E (19 ± 3 vs 12 ± 4 colonies/2 x 105 cells, p<0.05), and CFU-F formation (36 ± 11 vs 23 ± 7 colonies/2 x 106 cells, p<0.01). Similar results were obtained in TPO-treated group. In in-vitro study, we further analyzed the effect of PME (0–500 ug/ml) on mouse CFU-F formation. The results showed that PME at 100–500 ug/ml significantly enhanced CFU-F formation (p<0.05, n=6). Our studies showed that PME enhances thrombopoiesis in vivo and the growth of bone marrow stromal cells in vitro. Therefore, we speculate that the thrombopoietic activity of PME may be mediated via promoting the bone marrow stromal cells. Although TPO has been effective as an agent for the recovery of platelet production after the onset of thrombocytopenia, long-term clinical usage of TPO may induce potential side effects such as thrombosis. Here we reported that the effect of PME is comparable with that of TPO on hematopoiesis and the production of platelets.

scholarly journals Two Caenorhabditis elegans calponin-related proteins have overlapping functions to maintain cytoskeletal integrity and are essential for reproduction

2020 ◽  
Author(s):  
Shoichiro Ono ◽  
Kanako Ono
Keyword(s):  
Caenorhabditis Elegans ◽  
Actin Filaments ◽  
Body Wall ◽  
The Body ◽  
Body Wall Muscle ◽  
Related Protein ◽  
Somatic Gonad ◽  
Related Proteins

AbstractMulticellular organisms have multiple genes encoding calponins and calponin-related proteins, and some of these are known to regulate actin cytoskeletal dynamics and contractility. However, functional similarities and differences among these proteins are largely unknown. In the nematode Caenorhabditis elegans, UNC-87 is a calponin-related protein with seven calponin-like (CLIK) motifs and is required for maintenance of contractile apparatuses in muscle cells. Here, we report that CLIK-1, another calponin-related protein that also contains seven CLIK motifs, has an overlapping function with UNC-87 to maintain actin cytoskeletal integrity in vivo and has both common and different actin-regulatory activities in vitro. CLIK-1 is predominantly expressed in the body wall muscle and somatic gonad, where UNC-87 is also expressed. unc-87 mutation causes cytoskeletal defects in the body wall muscle and somatic gonad, whereas clik-1 depletion alone causes no detectable phenotypes. However, simultaneous depletion of clik-1 and unc-87 caused sterility due to ovulation failure by severely affecting the contractile actin networks in the myoepithelial sheath of the somatic gonad. In vitro, UNC-87 bundles actin filaments. However, CLIK-1 binds to actin filaments without bundling them and is antagonistic to UNC-87 in filament bundling. UNC-87 and CLIK-1 share common functions to inhibit cofilin binding and allow tropomyosin binding to actin filaments, suggesting that both proteins stabilize actin filaments. Thus, partially redundant functions of UNC-87 and CLIK-1 in ovulation is likely mediated by their common actin-regulatory activities, but their distinct activities in actin bundling suggest that they also have different biological functions.

scholarly journals Verification of the Field Productivity and Bioequivalence of a Medicinal Plant (Polygonum multiflorum) Developed Using an In Vitro Culture Method

Plants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 1280
Author(s):  
Yong-Goo Kim ◽  
Richard Komakech ◽  
Dae Hui Jeong ◽  
Kwonseok Jeon ◽  
Yunmi Park ◽  
...  
Keyword(s):  
Near Infrared ◽  
Culture Method ◽  
Culture Technique ◽  
Oriental Medicine ◽  
Polygonum Multiflorum ◽  
Perennial Plant ◽  
Plant Parts ◽  
Beneficial Effects ◽  
Root Tissues

Polygonum multiflorum Thunb. is a perennial plant that belongs to Polygonaceae. Root tissues are the main plant parts used as medicinal herbs in Korean oriental medicine. The P. multiflorum tuber is well known for its medicinal properties in Korean oriental medicine, and it contains a number of useful substances (secondary metabolites of emodin, 2,3,5,4′-tetrahydroxystilbene-2-O-β-d-glucoside (TSG), etc.) that are increasing in demand, as several studies show that they have beneficial effects on the human body. In this study, the production volumes and useful material content differences between cultured P. multiflorum seedlings (culture seedlings: CSs), which had been grown using a tissue culture technique under optimized conditions, and existing varieties in circulation (seed seedlings: SSs) were determined using a long-term field test. The growth characteristics of the underground parts were investigated by harvesting the tuberous roots (medicinal parts) after 1 year, and the results showed that the fresh and dry weights of the CS tubers were higher than those of the SS tubers. However, the SS rootlets had higher fresh and dry weights than the CS rootlets. A liquid chromatography-mass spectrometry component analysis of the P. multiflorum tubers and a Fourier transform near-infrared spectrophotometer analysis of the roots were undertaken. The results showed that the levels of TSG, which is a medicinal substance produced by P. multiflorum, were higher in the CSs than in the SSs, but the differences were not significant. The CS results from this study will inform future studies on the mass production of P. multiflorum in the field because the medicinal area was greater in CSs than in SSs.

scholarly journals Obesity-related proteins score as a potential marker of breast cancer risk

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sha Diao ◽  
Xueyao Wu ◽  
Xiaofan Zhang ◽  
Yu Hao ◽  
Bin Xu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Luminal Breast Cancer ◽  
Obese Women ◽  
Related Protein ◽  
Step Method ◽  
Potential Marker ◽  
Related Proteins

AbstractThere is strong evidence to suggest that obesity-related proteins play a key role in pathways that are related to breast cancer. In this study, we aimed to establish a robust obesity-related protein score (ORPS) that could be used to assess breast cancer risk. Based on evidence from high-quality systematic reviews and population studies, we selected nine such proteins that are stable in vitro, and measured their circulating concentrations by ELISA in a case–control study conducted in Chengdu, Sichuan, China, with 279 breast cancer cases and 260 healthy controls. Two obesity-related protein scores (ORPS) were calculated using a three-step method, with linear-weighted summation, and the one with a larger area under the curve was chosen for further evaluation. As a result, ORPS (PS5pre or PS4post) was positively correlated with breast cancer risk (premenopausal: OR≤63 VS >63 3.696, 95% CI 2.025–6.747; postmenopausal: OR≤38 VS >38 7.100, 95% CI 3.134–16.084), and represented a better risk predictor among obese women compared to non-obese in pre- and postmenopausal women. Among different molecular subtypes, ORPS was positively correlated with Luminal breast cancer, with additionally positive association with triple-negative breast cancer in premenopausal women. The ORPS might be a potential marker of breast cancer risk among Chinese women.

scholarly journals Two Caenorhabditis elegans calponin-related proteins have overlapping functions that maintain cytoskeletal integrity and are essential for reproduction

2020 ◽  
Vol 295 (34) ◽  
pp. 12014-12027
Author(s):  
Shoichiro Ono ◽  
Kanako Ono
Keyword(s):  
Caenorhabditis Elegans ◽  
Actin Filaments ◽  
Body Wall ◽  
The Body ◽  
Body Wall Muscle ◽  
Related Protein ◽  
Somatic Gonad ◽  
Related Proteins

Multicellular organisms have multiple genes encoding calponins and calponin-related proteins, some of which are known to regulate actin cytoskeletal dynamics and contractility. However, the functional similarities and differences among these proteins are largely unknown. In the nematode Caenorhabditis elegans, UNC-87 is a calponin-related protein with seven calponin-like (CLIK) motifs and is required for maintenance of contractile apparatuses in muscle cells. Here, we report that CLIK-1, another calponin-related protein that also contains seven CLIK motifs, functionally overlaps with UNC-87 in maintaining actin cytoskeletal integrity in vivo and has both common and different actin-regulatory activities in vitro. We found that CLIK-1 is predominantly expressed in the body wall muscle and somatic gonad in which UNC-87 is also expressed. unc-87 mutation caused cytoskeletal defects in the body wall muscle and somatic gonad, whereas clik-1 depletion alone caused no detectable phenotypes. However, simultaneous clik-1 and unc-87 depletion caused sterility because of ovulation failure by severely affecting the contractile actin networks in the myoepithelial sheath of the somatic gonad. In vitro, UNC-87 bundled actin filaments, whereas CLIK-1 bound to actin filaments without bundling them and antagonized UNC-87–mediated filament bundling. We noticed that UNC-87 and CLIK-1 share common functions that inhibit cofilin binding and allow tropomyosin binding to actin filaments, suggesting that both proteins stabilize actin filaments. In conclusion, partially redundant functions of UNC-87 and CLIK-1 in ovulation are likely mediated by their common actin-regulatory activities, but their distinct actin-bundling activities suggest that they also have different biological functions.

scholarly journals Dietary Scopoletin Ameliorates Diabetes-Associated Impairment of Bone Turnover via Activation of Bone Morphogenetic Protein-2 Pathway

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 342-342
Author(s):  
Eun-Jung Lee ◽  
Young-Hee Kang
Keyword(s):  
Bone Remodeling ◽  
High Glucose ◽  
In Vitro Study ◽  
Science Research ◽  
Bone Diseases ◽  
Bone Morphogenetic Protein 2 ◽  
Raw 264.7 Cells ◽  
Increased Risk

Abstract Objectives Diabetes induces bone deteriorateion leading to osteopenia, increased risk of fracture and osteoporosis. Thus, diabetes-induced bone fragility has been recently recognized as a diabetic complication. However, the pathophysiological effects of hyperglycemia on osteoclastogenesis and osteoblastogenesis remain unclear. Scopoletin, a coumarin family, is naturally found at notably high concentrations in chicory, leaves of stinging nettle, passion flower and noni. The purpose of this study was to identify that scopoletin was capable of preventing diabetic impairment of bone remodeling through BMP-2 pathway. Methods The in vitro study employed osteoblastic MC3T3-E1 cells that were exposed to 33 mM glucose in the presence of 1–20 μM scopoletin. In addition, murine macrophage Raw 264.7 cells were incubated with RANKL for differentiation to multi-nucleated osteoclasts and treated with 33 mM glucose for 5 days in the presence of 1–20 μM scopoletin. The in vivo study was conducted with the db/db mice that were orally administrated 10 mg/kg scopoletin daily for 10 weeks. Results High glucose diminished TRAP activity and bone resorption in RANKL-differentiated osteoclasts, indicating that osteoclast activation may be impaired under diabetic conditions. In contrast, scopoletin elevated osteoclastic differentiation and activation reduced by glucose. On the other hand, high glucose attenuated the ALP activity of osteoblastic cells, which was enhanced by treating 1–20 μM scopoletin to cells. Oral administration of scopoletin elevated plasma levels of osteoprotegerin, RANKL and osteocalcin reduced in diabetic mice, and increased trabecular bone formation and ephiphyseal disc thickness of growing bone. Finally, scopoletin enhanced the induction of Runx2 and BMP-2 in osteoblasts dampened by high glucose. Conclusions Scopoletin improved aberrant bone remodeling in diabetic osteoblasts and osteoclasts through induction of Runx2 and BMP-2. These findings suggest the possibility that scopoletin could be a potential agent for the treatment of diabetes-associated bone diseases. Funding Sources This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (2019R1A2C1003218), and was supported by Basic Science Research Program through NRF funded by the Ministry of Education (2020R1A6A3A0110009611).

scholarly journals Parathyroid Hormone-Related Protein, Its Regulation of Cartilage and Bone Development, and Role in Treating Bone Diseases

2016 ◽  
Vol 96 (3) ◽  
pp. 831-871 ◽  
Author(s):  
T. John Martin
Keyword(s):  
Parathyroid Hormone ◽  
Bone Remodeling ◽  
Hormonal Regulation ◽  
Placental Transfer ◽  
Physiological Function ◽  
Bone Diseases ◽  
Endochondral Bone Formation ◽  
Related Protein ◽  
Amino Terminal ◽  
Parathyroid Hormone Related Protein

Although parathyroid hormone-related protein (PTHrP) was discovered as a cancer-derived hormone, it has been revealed as an important paracrine/autocrine regulator in many tissues, where its effects are context dependent. Thus its location and action in the vasculature explained decades-long observations that injection of PTH into animals rapidly lowered blood pressure by producing vasodilatation. Its roles have been specified in development and maturity in cartilage and bone as a crucial regulator of endochondral bone formation and bone remodeling, respectively. Although it shares actions with parathyroid hormone (PTH) through the use of their common receptor, PTHR1, PTHrP has other actions mediated by regions within the molecule beyond the amino-terminal sequence that resembles PTH, including the ability to promote placental transfer of calcium from mother to fetus. A striking feature of the physiology of PTHrP is that it possesses structural features that equip it to be transported in and out of the nucleus, and makes use of a specific nuclear import mechanism to do so. Evidence from mouse genetic experiments shows that PTHrP generated locally in bone is essential for normal bone remodeling. Whereas the main physiological function of PTH is the hormonal regulation of calcium metabolism, locally generated PTHrP is the important physiological mediator of bone remodeling postnatally. Thus the use of intermittent injection of PTH as an anabolic therapy for bone appears to be a pharmacological application of the physiological function of PTHrP. There is much current interest in the possibility of developing PTHrP analogs that might enhance the therapeutic anabolic effects.

Sign in / Sign up

Export Citation Format

Share Document