Cellulose Acetate Nanofibers: Incorporating Hydroxyapatite (HA), HA/Berberine or HA/Moghat Composites, as Scaffolds to Enhance In Vitro Osteoporotic Bone Regeneration

The specific objective of this study was to stabilize a simple valid method to prepare pure nanorod hydroxyapatite (HA) mixed with berberine chloride (BER) and Moghat water extract (ME) as composites for incorporation into cellulose acetate (CA) nanofibers to be used as novel bone scaffolds and to determine their efficacy in bone regeneration process In Vitro. Preparation of HA/BER and HA/ME composites were performed by mixing powders using the ball-milling machine. The HA, HA/BER, and HA/ME composites at a concentration of 6.25, 12.5, 25, 50, 100, and 200 mg were mixed with CA solution (13%), then the fiber was formed using electrospinning technique. The properties of the obtained CA fibers were investigated (SEM, TEM, EDX, FTIR, TGA, water uptake, porosity, and mechanical tests). The efficacy of HA and HA composites loaded into CA nanofiber on osteoblast and osteoclast differentiation were measured by tacking ALP, osteocalcin, TRAcP, calcium, and total protein concentration. Moreover, their effects on cell differentiation (CD90 and PARP- ɣ) and death markers (GSK3b, MAPK, Wnt-5 and β-catenin) were evaluated by using ELISA and qPCR. The obtained TEM results indicated that the continuous CA and CA/HA composites electrospun fibers have ultrafine fiber diameters of about 200 nm and uniform distribution of discrete n-HA clusters throughout. In addition, hydrocortisone (HCT) was found to increase the formation of adipocytes and osteoclastic markers CD90 and p38-MAPK which indicated the bone lose process take placed. Treatment with CA loaded with HA, HA/BER or HA/ME decreased CD90, Wnt-5, PARP- ɣ, GSK3b and p38-MAPK associated elevation of osteogenic markers: ALP and osteocalcin. Moreover, HCT overexpressed RANKL and down expressed Osterix gene. Treatment with CA/HA/BER or CA/HA/ME downregulated RANKL and upregulated Osterix associated with a reduction in RANKL/OPG ratio, at p < 0.05. In conclusion, novel CA composite nanofibers (CA/HA/BER and CA/HA/ME) reversed the HCT adverse effect on osteoblast cell death through canonical and non-canonical pathways regulated by Wnt/β-catenin and Wnt/Ca(2+) pathways. Furthermore, our data confirmed that the novel scaffolds create a crosstalk between RUNX-2, RANKL, p38-MAPK, and Wnt signals which positively impact bone regeneration process. Treatment with CA/HA/BER is better compared to the treatment with CA/HA/ME. Nevertheless, both are considered as alternative biomaterial scaffolds with a potential for biomedical applications in the field of bone tissue engineering.

Download Full-text

Artemisia capillaris Alleviates Bone Loss by Stimulating Osteoblast Mineralization and Suppressing Osteoclast Differentiation and Bone Resorption

The American Journal of Chinese Medicine ◽

10.1142/s0192415x16500944 ◽

2016 ◽

Vol 44 (08) ◽

pp. 1675-1691 ◽

Cited By ~ 4

Author(s):

Chung-Jo Lee ◽

Ki-Shuk Shim ◽

Jin Yeul Ma

Keyword(s):

Bone Resorption ◽

Bone Loss ◽

Osteoclast Differentiation ◽

Water Extract ◽

Osteoclast Formation ◽

Bone Diseases ◽

Osteoporotic Bone ◽

Nuclear Factor ◽

Artemisia Capillaris

Artemisia capillaris has been used to treat jaundice and relieve high liver-heat in traditional medicine. In this study, we found that the administration of a water extract from A. capillaris (WEAC) to the receptor activator of nuclear factor kappa-B ligand (RANKL)-induced bone loss model significantly prevents osteoporotic bone loss, increasing bone volume/trabecular volume by 22% and trabecular number by 24%, and decreasing trabecular separation by 29%. WEAC stimulated in vitro osteoblast mineralization from primary osteoblasts in association with increasing expression of osterix, nuclear factor of activated T cells cytoplasmic 1, and activator protein-1, as well as phosphorylation of extracellular signal-regulated kinase. In contrast to the anabolic effect of WEAC, WEAC significantly suppressed in vitro osteoclast formation from bone marrow macrophages by inhibiting the RANKL signaling pathways and bone resorption by downregulating the expression of resorption markers. Therefore, this study demonstrated that WEAC has a beneficial effect on bone loss through the regulation of osteoblast mineralization, as well as osteoclast formation and bone resorption. These results suggest that A. capillaris may be a promising herbal candidate for therapeutic agents to treat or prevent osteoporotic bone diseases.

Download Full-text

A multi-functionalized calcitriol sustainable delivery system for promoting osteoporotic bone regeneration both in vitro and in vivo

Applied Materials Today ◽

10.1016/j.apmt.2020.100906 ◽

2021 ◽

Vol 22 ◽

pp. 100906

Author(s):

Zhichao Hu ◽

Qian Tang ◽

Deyi Yan ◽

Gang Zheng ◽

Mingbao Gu ◽

...

Keyword(s):

Bone Regeneration ◽

Delivery System ◽

Osteoporotic Bone

Download Full-text

Microporous polysaccharide multilayer coated BCP composite scaffolds with immobilised calcitriol promote osteoporotic bone regeneration both in vitro and in vivo

Theranostics ◽

10.7150/thno.29566 ◽

2019 ◽

Vol 9 (4) ◽

pp. 1125-1143 ◽

Cited By ~ 5

Author(s):

Qian Tang ◽

Zhichao Hu ◽

Haiming Jin ◽

Gang Zheng ◽

XingFang Yu ◽

...

Keyword(s):

Bone Regeneration ◽

Osteoporotic Bone ◽

Composite Scaffolds

Download Full-text

Electrospun Poly(γ–glutamic acid)/β–Tricalcium Phosphate Composite Fibrous Mats for Bone Regeneration

Polymers ◽

10.3390/polym11020227 ◽

2019 ◽

Vol 11 (2) ◽

pp. 227 ◽

Cited By ~ 8

Author(s):

Chun-Hsu Yao ◽

Shau-Pei Yang ◽

Yueh-Sheng Chen ◽

Kuo-Yu Chen

Keyword(s):

Glutamic Acid ◽

Bone Regeneration ◽

Tricalcium Phosphate ◽

Bone Growth ◽

Weight Ratio ◽

Cranial Bone ◽

Cross Linking ◽

Scanning Electron Micrographs ◽

Electrospinning Technique

A poly(γ–glutamic acid)/β–tricalcium phosphate (γ–PGA/β–TCP) composite fibrous mat was fabricated using the electrospinning technique as a novel bone substitute. The mat was then cross-linked with cystamine in the presence of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide to improve its water-resistant ability. Scanning electron micrographs revealed that the γ–PGA/β–TCP fibers had a uniform morphology with diameters ranging from 0.64 ± 0.07 µm to 1.65 ± 0.16 µm. The average diameter of the fibers increased with increasing cross-linking time. Moreover, increasing the cross-linking time and decreasing the γ–PGA/β–TCP weight ratio decreased the swelling ratio and in vitro degradation rate of the composite fibrous mat. In vitro experiments with osteoblast-like MG-63 cells demonstrated that the mat with a γ–PGA/β–TCP weight ratio of 20 and cross-linked time of 24 h had a higher alkaline phosphatase activity and better cell adhesion. Furthermore, the rat cranial bone defect was created and treated with the γ–PGA/β–TCP composite fibrous mat to evaluate its potential in bone regeneration. After 8 weeks of implantation, micro computed tomography showed that the γ–PGA/β–TCP composite fibrous mat promoted new bone growth. These observations suggest that the γ–PGA/β–TCP composite fibrous mat has a potential application in bone tissue engineering.

Download Full-text

Anti–IL-20 monoclonal antibody inhibits the differentiation of osteoclasts and protects against osteoporotic bone loss

Journal of Experimental Medicine ◽

10.1084/jem.20102234 ◽

2011 ◽

Vol 208 (9) ◽

pp. 1849-1861 ◽

Cited By ~ 47

Author(s):

Yu-Hsiang Hsu ◽

Wei-Yu Chen ◽

Chien-Hui Chan ◽

Chih-Hsing Wu ◽

Zih-Jie Sun ◽

...

Keyword(s):

Monoclonal Antibody ◽

Bone Loss ◽

Therapeutic Potential ◽

Osteoclast Differentiation ◽

Bone Destruction ◽

Osteoporotic Bone ◽

Mineral Density

IL-20 is a proinflammatory cytokine of the IL-10 family that is involved in psoriasis, rheumatoid arthritis, atherosclerosis, and stroke. However, little is known about the role of IL-20 in bone destruction. We explored the function of IL-20 in osteoclastogenesis and the therapeutic potential of anti–IL-20 monoclonal antibody 7E for treating osteoporosis. Higher serum IL-20 levels were detected in patients with osteopenia and osteoporosis and in ovariectomized (OVX) mice. IL-20 mediates osteoclastogenesis by up-regulating the receptor activator of NF-κB (RANK) expression in osteoclast precursor cells and RANK ligand (RANKL) in osteoblasts. 7E treatment completely inhibited osteoclast differentiation induced by macrophage colony-stimulating factor (M-CSF) and RANKL in vitro and protected mice from OVX-induced bone loss in vivo. Furthermore, IL-20R1–deficient mice had significantly higher bone mineral density (BMD) than did wild-type controls. IL-20R1 deficiency also abolished IL-20–induced osteoclastogenesis and increased BMD in OVX mice. We have identified a pivotal role of IL-20 in osteoclast differentiation, and we conclude that anti–IL-20 monoclonal antibody is a potential therapeutic for protecting against osteoporotic bone loss.

Download Full-text

Microporous polysaccharide multilayer coated BCP composite scaffolds with immobilised calcitriol promote osteoporotic bone regeneration both in vitro and in vivo: Erratum

Theranostics ◽

10.7150/thno.61641 ◽

2021 ◽

Vol 11 (13) ◽

pp. 6524-6525

Author(s):

Qian Tang ◽

Zhichao Hu ◽

Haiming Jin ◽

Gang Zheng ◽

XingFang Yu ◽

...

Keyword(s):

Bone Regeneration ◽

Osteoporotic Bone ◽

Composite Scaffolds

Download Full-text

Electrospun acetaminophen-loaded cellulose acetate nanofibers fabricated using an epoxy-coated spinneret

e-Polymers ◽

10.1515/epoly-2015-0088 ◽

2015 ◽

Vol 15 (5) ◽

pp. 311-315 ◽

Cited By ~ 5

Author(s):

Xia Wang ◽

Xiao-Yan Li ◽

Ying Li ◽

Hua Zou ◽

Deng Guang Yu ◽

...

Keyword(s):

Stainless Steel ◽

Cellulose Acetate ◽

Amorphous State ◽

Electrospun Nanofibers ◽

Electrospinning Technique ◽

Stainless Steel Capillary ◽

Dissolution Tests ◽

Model Drug ◽

Functional Nanofibers

AbstractThis paper reports the investigation about the usage of an epoxy (EP)-coated spinneret for the preparation of medicated electrospun nanofibers. Cellulose acetate (CA) and acetaminophen (APAP) were used as the polymeric carrier and model drug, respectively. The electrospinning was undertaken using both EP-coated spinneret and traditional stainless steel capillary as spinnerets. According to the images from scanning electron microscopy, it is obvious that the nanofibers produced using the EP-coated spinneret had a finer diameter and a narrower size distribution (450±90 nm) than nanofibers fabricated using stainless steel equivalent (660±180 nm). In vitro dissolution tests revealed that the sustained-release profiles of nanofibers from the EP-coated spinneret were superior to those of their stainless steel equivalents, although APAP existed in a similar amorphous state in both nanofibers. Because the EP-coated material can exploit the electrical forces more effectively than its steel analogue, it can enhance the electrospinning technique for producing polymeric functional nanofibers.

Download Full-text

Alpinia officinarum Stimulates Osteoblast Mineralization and Inhibits Osteoclast Differentiation

The American Journal of Chinese Medicine ◽

10.1142/s0192415x16500701 ◽

2016 ◽

Vol 44 (06) ◽

pp. 1255-1271 ◽

Cited By ~ 7

Author(s):

Ki-Shuk Shim ◽

Chung-Jo Lee ◽

Nam-Hui Yim ◽

Min Jung Gu ◽

Jin Yeul Ma

Keyword(s):

Transcription Factor ◽

Osteoclast Differentiation ◽

Water Extract ◽

Bone Diseases ◽

Bone Morphogenetic Protein 2 ◽

Mrna Levels ◽

Nuclear Factor ◽

Alizarin Red ◽

Alpinia Officinarum

Alpinia officinarum rhizome has been used as a traditional herbal remedy to treat inflammatory and internal diseases. Based on the previously observed inhibitory effect of A. officinarum rhizome in an arthritis model, we evaluated whether a water extract of A. officinarum rhizome (WEAO) would enhance in vitro osteoblast mineralization using calvarial osteoblast precursor cells or would inhibit in vitro osteoclast differentiation and bone resorption using bone marrow derived macrophages. In osteoblasts, WEAO enhanced the mRNA levels of transcription factor (runt-related transcription factor 2, smad1, smad5, and junB) and marker (bone morphogenetic protein-2, collagen type 1alpha1, and osteocalcin) genes related to osteoblast mineralization, consistent with increased alizarin red S staining intensity. WEAO markedly inhibited osteoclast differentiation by suppressing the receptor activator for nuclear factor-[Formula: see text]B ligand-induced downregulation of inhibitor of DNA binding 2 and V-maf musculoaponeurotic fibrosarcoma oncogene homolog B and the phosphorylation of c-Jun N-terminal kinase, p38, nuclear factor-[Formula: see text]B, c-Src, and Bruton’s tyrosine kinase to induce nuclear factor of activated T cells cytoplasmic 1 expression. WEAO also suppressed the resorbing activity of mature osteoclasts by altering actin ring formation. Therefore, the results of this study demonstrate that WEAO stimulates osteoblast mineralization and inhibits osteoclast differentiation. Thus, WEAO may be a promising herbal candidate to treat or prevent pathological bone diseases by regulating the balance between osteoclast and osteoblast activity.

Download Full-text

Inhibition of Osteoclast Differentiation by Ginsenoside Rg3 in RAW264.7 Cells via RANKL, JNK and p38 MAPK Pathways Through a Modulation of Cathepsin K: An In Silico and In Vitro Study

Phytotherapy Research ◽

10.1002/ptr.5374 ◽

2015 ◽

Vol 29 (9) ◽

pp. 1286-1294 ◽

Cited By ~ 18

Author(s):

Muhammad Hanif Siddiqi ◽

Muhammad Zubair Siddiqi ◽

Sera Kang ◽

Hae Yong Noh ◽

Sungeun Ahn ◽

...

Keyword(s):

P38 Mapk ◽

In Silico ◽

Osteoclast Differentiation ◽

In Vitro Study ◽

Cathepsin K ◽

Vitro Study ◽

Raw264.7 Cells ◽

Ginsenoside Rg3 ◽

Mapk Pathways

Download Full-text

Anti-Osteoporotic Effects of Combined Extract of Lycii Radicis Cortex and Achyranthes japonica in Osteoblast and Osteoclast Cells and Ovariectomized Mice

Nutrients ◽

10.3390/nu11112716 ◽

2019 ◽

Vol 11 (11) ◽

pp. 2716 ◽

Cited By ~ 3

Author(s):

Eunkuk Park ◽

Jeonghyun Kim ◽

Subin Yeo ◽

Eunguk Lim ◽

Chun Whan Choi ◽

...

Keyword(s):

Bone Loss ◽

Osteoclast Differentiation ◽

Osteoporotic Bone ◽

Osteoblastic Cell ◽

Mouse Bone Marrow ◽

Osteoblastic Cell Line ◽

Ovariectomized Mice ◽

Achyranthes Japonica

Osteoporosis is characterized by low bone density and quality with high risk of bone fracture. Here, we investigated anti-osteoporotic effects of natural plants (Lycii Radicis Cortex (LRC) and Achyranthes japonica (AJ)) in osteoblast and osteoclast cells in vitro and ovariectomized mice in vivo. Combined LRC and AJ enhanced osteoblast differentiation and mineralized bone-forming osteoblasts by the up-regulation of bone metabolic markers (Alpl, Runx2 and Bglap) in the osteoblastic cell line MC3T3-E1. However, LRC and AJ inhibited osteoclast differentiation of monocytes isolated from mouse bone marrow. In vivo experiments showed that treatment of LRC+AJ extract prevented OVX-induced trabecular bone loss and osteoclastogenesis in an osteoporotic animal model. These results suggest that LRC+AJ extract may be a good therapeutic agent for the treatment and prevention of osteoporotic bone loss.

Download Full-text