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1.
World Neurosurg ; 2024 Jun 18.
Article En | MEDLINE | ID: mdl-38901485

Full-endoscopic lumbar interbody fusion (FELIF) is a critical yet challenging procedure. However, extensive analyses of discectomy and cartilage endplate preparation techniques are limited. This can be attributed to the lack of universal protocols owing to diverse surgical practices and equipment preferences. Therefore, this narrative review presents a comprehensive overview of discectomy and cartilage endplate preparation techniques in FELIF. A literature search of the PubMed, Embase, and Google Scholar databases in December 2023 retrieved 490 studies, of which 53 met the pre-defined inclusion criteria, and 1373 patients were included in the analyses. Spinal endoscopic disc and cartilage endplate removal can be categorized into two main types: removal under direct endoscopic visualization and removal under radiographic guidance with the protection of a working sheath following the endoscope's removal. Removal under direct visualization ensures the safety and precision of the procedure. Radiographic guidance can enhance the efficiency of the removal process. Specially designed instruments can be utilized through the narrow working channels of spinal endoscopes for the scraping surgery. Moreover, many traditional spinal endoscopic instruments, through specific techniques and manipulations, can also aid in cartilage removal. The approaches and techniques vary significantly among physicians, but overall, these instruments and techniques aim to achieve a safe and efficient disc-scraping outcome. Thus, this review may offer a comprehensive guidance to surgeons in selecting the most efficient practices for FELIF. Uniform procedural protocols are needed to ensure broader adoption and standardized practice.

2.
J Clin Med ; 13(7)2024 Mar 26.
Article En | MEDLINE | ID: mdl-38610675

Background: This study investigates the efficacy of the Cervical Endoscopic Unilateral Laminoforaminotomy for Bilateral Decompression (CE-ULFBD) technique in treating cervical myeloradiculopathy, primarily caused by degenerative spondylosis. Traditionally managed through multisegmental anterior cervical discectomy and fusion (ACDF) or laminoplasty combined with foraminotomy, this condition has recently experienced a promising shift towards minimally invasive approaches, particularly endoscopic spinal decompression. While empirical evidence is still emerging, these techniques show potential for effective treatment. Method: The objective was to evaluate the outcomes of CE-ULFBD in achieving single or multilevel bilateral foraminal and central decompression, emphasizing the reduction of injury to posterior cervical muscles and the associated postoperative neck soreness common in conventional procedures. This paper delineates the surgical procedures involved in CE-ULFBD and presents the clinical outcomes of nine patients diagnosed with myeloradiculopathy due to severe cervical stenosis. Result: Assessments were conducted using the Visual Analogue Scale (VAS) for neck and arm pain and the Modified Japanese Orthopaedic Association scale (mJOA) for the activity measurement of daily living. Results indicated a considerable decrease in pain levels according to the VAS, coupled with significant improvements in functional capacities as measured by the mJOA scale. Additionally, no major postoperative complications were noted during the follow-up period. Conclusion: The study concludes that CE-ULFBD is a safe and effective approach for the treatment of cervical myeloradiculopathy resulting from severe cervical stenosis, offering a viable and less invasive alternative to traditional decompressive surgeries.

3.
Eur Spine J ; 33(2): 417-428, 2024 Feb.
Article En | MEDLINE | ID: mdl-37389696

PURPOSE: Full-endoscopic lumbar interbody fusion (FELIF) is a new-generation treatment for spondylolisthesis. However, owing to their unique characteristics, the two main endoscopic fusion trajectories, the trans-Kambin and posterolateral approaches, have important limitations. Herein, we aimed to introduce a new technique called Kambin Torpedo FELIF (KT-FELIF). METHODS: The KT-FELIF technique is based on the trans-Kambin approach. It additionally completes ipsilateral total facetectomy and contralateral direct decompression. Thus, this novel technique combines the advantages of the trans-Kambin and posterolateral approaches. RESULTS: We reported on the indications and technical steps of KT-FELIF and provided intraoperative and animated videos to clarify the procedure. Short-term follow-up based on 3-month postoperative computed tomography and plain films images taken at least 3 months after surgery showed adequate bony decompression, a large bone graft contact area, and good intervertebral trabecular bone growth without radiolucent lines between the graft, cage, and end plate. The clinical results, such as ipsilateral and contralateral visual analog scale and Oswestry disability index values, gradually improved at 1 and 3 months postoperatively. No complications were observed. CONCLUSIONS: KT-FELIF is a promising FELIF technique for achieving bilateral direct decompression through a unilateral approach while accomplishing thorough discectomy and endplate preparation.


Endoscopy , Research , Humans , Bone Plates , Bone Transplantation , Cancellous Bone
4.
Int J Biol Sci ; 19(16): 5275-5289, 2023.
Article En | MEDLINE | ID: mdl-37928270

Osteoarthritis (OA) is a prevalent joint disease commonly associated with aging and obesity, which can lead to pain, stiffness, joint dysfunction, and disability. Omentin-1 (also called intelectin-1) is a newly discovered adipokine, which plays a protective role in suppressing the secretion of pro-inflammatory cytokines. Based on data from the Gene Expression Omnibus (GEO) dataset and clinical samples obtained at our institution revealed, determined that omentin-1 and IL-4 (an anti-inflammatory cytokine) levels were significantly lower in OA patients than in normal controls. Omentin-1 was shown to induce IL-4-depedent anti-inflammatory responses and M2 macrophage polarization in OA synovial fibroblasts via the PI3K, ERK, and AMPK pathways. Administering omentin-1 was shown to block cartilage degradation and bone erosion resulting from anterior cruciate ligament transection by inhibiting the production of pro-inflammatory cytokines and promoting M2 macrophage polarization in vivo. Our findings indicate omentin-1 as a promising therapeutic avenue for the treatment for OA.


Cytokines , Interleukin-4 , Macrophages , Osteoarthritis , Humans , Cytokines/metabolism , Interleukin-4/immunology , Macrophages/immunology , Osteoarthritis/immunology
5.
Biochem Pharmacol ; 218: 115853, 2023 12.
Article En | MEDLINE | ID: mdl-37832794

Osteosarcoma is a malignant tumor with high metastatic potential, such that the overall 5-year survival rate of patients with metastatic osteosarcoma is only 20%. Therefore, it is necessary to unravel the mechanisms of osteosarcoma metastasis to identify predictors of metastasis by which to develop new therapies. Fibroblast growth factor 2 (FGF2) is a growth factor involved in embryonic development, cell migration, and proliferation. The overexpression of FGF2 and FGF receptors (FGFRs) has been shown to enhance cancer cell proliferation in lung, breast, gastric, and prostate cancers as well as melanoma. Nonetheless, the roles of FGF2 and FGFRs in human osteosarcoma cells remain unknown. In the present study, we found that FGF2 was overexpressed in human osteosarcoma sections and correlated with lung metastasis. Treatment of FGF2 induced migration activity, invasion activity, and intercellular adhesion molecule (ICAM)-1 expression in osteosarcoma cells. In particular, the downregulation or antagonism of FGFR1-4 suppressed FGF2-induced ICAM-1 expression and cancer cell migration. Furthermore, FGFR1, FGFR2, FGFR3, and FGFR4 were involved in FGF2-induced the phospholipase Cß/protein kinase Cα/proto-oncogene c-Src signaling pathway and triggered c-Jun nuclear translocation. Subsequent c-Jun upregulation of activator protein-1 transcription activity on the ICAM-1 promoter led to an increased migration of osteosarcoma cells. Moreover, the knockdown of endogenous FGF2 suppressed ICAM-1 expression and migration of osteosarcoma cells. These findings suggest that FGF2/FGFR1-4 signaling promotes metastasis via its direct downstream target gene ICAM-1, revealing a novel potential therapeutic target for osteosarcoma.


Bone Neoplasms , Osteosarcoma , Humans , Male , Bone Neoplasms/genetics , Fibroblast Growth Factor 2/genetics , Intercellular Adhesion Molecule-1 , Osteosarcoma/genetics , Osteosarcoma/pathology , Receptor, Fibroblast Growth Factor, Type 1/genetics , Signal Transduction
6.
J Pineal Res ; 75(1): e12872, 2023 Aug.
Article En | MEDLINE | ID: mdl-37057370

Chondrosarcoma has a high propensity to metastasize and responds poorly to chemotherapy and radiation treatment. The enzymatic activity of matrix metalloproteinases (MMPs) is very important in chondrosarcoma metastasis. Melatonin exhibits anticarcinogenic activity in many types of cancers by suppressing the expression of certain MMP family members, but this has not yet been clearly determined in chondrosarcoma. Our study demonstrates that MMP7 plays an essential role in chondrosarcoma cell proliferation, migration, and anoikis resistance. We also found that MMP7 is highly expressed in chondrosarcomas. Our in vitro and in vivo investigations show that melatonin strongly inhibits chondrosarcoma cell proliferation, migration, and anoikis resistance by directly suppressing MMP7 expression. Melatonin reduced MMP7 synthesis by promoting levels of miR-520f-3p expression, which were downregulated in human chondrosarcoma tissue samples. Pharmacological inhibition of miR-520f-3p markedly reversed the effects of melatonin upon chondrosarcoma proliferation and metastasis. Thus, our study suggests that melatonin has therapeutic potential for reducing the tumorigenesis and metastatic potential of chondrosarcoma via the miR-520f-3p/MMP7 axis.


Chondrosarcoma , Melatonin , MicroRNAs , Humans , MicroRNAs/genetics , Cell Line, Tumor , Melatonin/pharmacology , Matrix Metalloproteinase 7/metabolism , Cell Proliferation , Chondrosarcoma/drug therapy , Chondrosarcoma/genetics , Chondrosarcoma/metabolism , Cell Movement , Gene Expression Regulation, Neoplastic
7.
J Mech Behav Biomed Mater ; 138: 105669, 2023 02.
Article En | MEDLINE | ID: mdl-36634436

Self-expanding sinus stents are often used in functional endoscopic sinus surgery to treat inflamed sinuses. The PROPEL self-expanding sinus stent offers mechanical support to the sinus cavity to prevent restenosis. The stent is made of a bioabsorbable material (PLGA) that disappears after wound healing. However, complications such as foreign body sensation and severe stent migration/expulsion have been reported after implantation. Little is known about the contact characteristics of self-expanding sinus stents from when the stent is crimped into the insertion device through to deployment into the sinus cavity. This current study developed a test platform to analyze the biomechanical behavior of the stent during this process. Three common bioabsorbable materials, PLGA, PCL and Mg alloy, were evaluated to understand how the choice of material affects the biomechanical characteristics of self-expanding sinus stents. The results showed that the material can have a considerable influence on the contact characteristics during crimping and deployment. When crimped, the PLGA and Mg alloy stents showed much higher plastic strain and contact stress than the PCL stent. When deployed, the PCL stent had the largest contact area (4.3 mm2) and the lowest contact pressure (0.1 MPa) on the inner surface of the sinus canal. The results indicate that PCL could be a suitable choice for self-expanding sinus stents. This current study provides a method for observing the biomechanical characteristics of sinus stents during stent crimping and deployment.


Alloys , Biocompatible Materials , Stents , Finite Element Analysis , Wound Healing
8.
Front Immunol ; 13: 1004334, 2022.
Article En | MEDLINE | ID: mdl-36203618

Recent literature highlights the importance of microRNAs (miRNAs) functioning as diagnostic biomarkers and therapeutic agents in osteoarthritis (OA) and regulators of gene expression. In OA pathogenesis, cell adhesion molecules (CAMs), especially vascular cell adhesion protein 1 (VCAM-1), recruit monocyte infiltration to inflamed synovial tissues and thus accelerate OA progression. Up until now, little has been known about the regulatory mechanisms between miRNAs, long non-coding RNAs (lncRNAs) and VCAM-1 during OA progression. The evidence in this article emphasizes that the functional feature of miR-150-5p is an interaction with the lncRNA X-inactive specific transcript (XIST), which regulates VCAM-1-dependent monocyte adherence in OA synovial fibroblasts (OASFs). Levels of VCAM-1, CD11b (a monocyte marker) and XIST expression were higher in human synovial tissue samples and OASFs, while levels of miR-150-5p were lower in human OA synovial tissue compared with non-OA specimens. XIST enhanced VCAM-1-dependent monocyte adherence to OASFs. Upregulation of miR-150-5p inhibited the effects of XIST upon monocyte adherence. Administration of miR-150-5p effectively ameliorated OA severity in anterior cruciate ligament transection (ACLT) rats. The interaction of miR-150-5p and XIST regulated VCAM-1-dependent monocyte adherence and attenuated OA progression. Our findings suggest that miR-150-5p is a promising small-molecule therapeutic strategy for OA.


MicroRNAs , Osteoarthritis , RNA, Long Noncoding/metabolism , Animals , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Monocytes/metabolism , Osteoarthritis/metabolism , Osteoarthritis/therapy , RNA, Long Noncoding/genetics , Rats , Vascular Cell Adhesion Molecule-1
9.
J Orthop Surg Res ; 17(1): 335, 2022 Jun 28.
Article En | MEDLINE | ID: mdl-35765082

BACKGROUND: Osteolysis is one of the most prevalent clinical complications affecting people who undergo total joint replacement (TJR). Wedelolactone (WDL) is a coumestan compound derived from the Wedelia chinensis plant and has been demonstrated to exhibit anti-inflammatory properties. This study aimed to investigate the oral administration of WDL as a potential treatment for particle-induced osteolysis using a well-established mice calvarial disease model. METHODS: Thirty-two C57BL/6 J mice were randomized into four groups: Sham, vehicle, osteolysis group with oral WDL treatment for 4 weeks (WDL 4w), and osteolysis group treated for 8 weeks (WDL 8w). Micro-CT was used to quantitatively analyze the bone mineral density (BMD), bone volume/tissue volume (BV/TV) and trabecular bone thickness (Tb.Th). Osteoclast numbers were also measured from histological slides by two investigators who were blind to the treatment used. RESULTS: The results from micro-CT observation showed that BMD in the WDL 8w group improved significantly over the vehicle group (p < 0.05), but there was no significant difference between WDL 4w and 8w for BV/TV and Tb.Th. Osteoclast numbers in the WDL 4w group were also lower than the vehicle group (p < 0.05), but the difference between WDL 8w and 4w groups was not significant. CONCLUSIONS: Particle-induced osteolysis is an inevitable long-term complication after TJR. The results of this animal study indicate that an oral administration of WDL can help reduce the severity of osteolysis without adverse effects.


Osteolysis , Animals , Coumarins , Humans , Mice , Mice, Inbred C57BL , Osteolysis/chemically induced , Osteolysis/diagnostic imaging , Osteolysis/drug therapy , Plant Extracts/therapeutic use , Research Design
10.
Nanotoxicology ; 16(1): 1-15, 2022 02.
Article En | MEDLINE | ID: mdl-35085045

Graphene is a novel material which has recently been gaining great interest in the biomedical fields. Our previous study observed that graphene-derived particles help induce bone formation in a murine calvarial model. Here, we further developed a blended graphene-contained polycaprolactone (PCL/G) filament for application in a 3D-printed bone scaffold. Since implants are expected to be for long-term usage, in vitro cell culture and in vivo scaffold implants were evaluated in a critical-size bone defect calvarial model for over 60 weeks. Graphene greatly improved the mechanical strength by 30.2% compared to pure PCL. The fabricated PCL/G scaffolds also showed fine cell viability. In animal model, an abnormal electroencephalogram power spectrum and early signs of aging, such as hair graying and hair loss, were found in the group with a PCL/G scaffold compared to pure PCL scaffold. Neither of the abnormal symptoms caused death of all animals in both groups. The long-term use of graphene-derived biomaterials for in-vivo implants seems to be safe. But the comprehensive biosafety still needs further evaluation.


Graphite , Tissue Scaffolds , Animals , Biocompatible Materials , Graphite/toxicity , Mice , Osteogenesis , Polyesters/pharmacology , Skull
11.
Comput Math Methods Med ; 2021: 9934107, 2021.
Article En | MEDLINE | ID: mdl-34925548

OBJECTIVES: To determine whether feeding CircuCare to rats improves blood circulation, metabolism, immune regulation, endocrine activity, and oxidative stress. METHODS: 28 eight-week-old male Sprague-Dawley rats were evenly randomized into control and experimental groups. The control group was fed with ordinary drinking water, while the experimental group was fed with CircuCare at a daily dose of 93.75 mg per 300 g of body weight over eight weeks. Both groups were subjected to a swimming test, and blood samples were taken to observe any variations in various biochemical parameters before and after the test. Key Findings. The experimental group's mean swimming exhaustion duration was 53.2% longer and had a significantly higher lactic acid removal ratio. Their mean prostaglandin E2 level and mean glucose, cortisol, and glutathione level (30 minutes after swimming test) were also significantly higher. No undesirable impacts from CircuCare relating to general blood biochemistry values and bone mineral density were reported. CONCLUSIONS: The present results show that CircuCare can be safely used to increase stamina and exercise capability, expedite the metabolism of lactic acid, accelerate muscle repair, and promote the antioxidant activity of cells in rats.


Blood Circulation/drug effects , Drugs, Chinese Herbal/pharmacology , Metabolism/drug effects , Animals , Blood Glucose/drug effects , Blood Glucose/metabolism , Bone Density/drug effects , Carica/chemistry , Computational Biology , Drugs, Chinese Herbal/chemistry , Endocrine Glands/drug effects , Endocrine Glands/physiology , Immunity/drug effects , Lactic Acid/blood , Male , Models, Animal , Oxidative Stress/drug effects , Panax/chemistry , Physical Exertion/drug effects , Rats , Rats, Sprague-Dawley
12.
Front Immunol ; 12: 737990, 2021.
Article En | MEDLINE | ID: mdl-34659230

Angiogenesis is a critical process in the formation of new capillaries and a key participant in rheumatoid arthritis (RA) pathogenesis. The adipokine apelin (APLN) plays critical roles in several cellular functions, including angiogenesis. We report that APLN treatment of RA synovial fibroblasts (RASFs) increased angiopoietin-1 (Ang1) expression. Ang1 antibody abolished endothelial progenitor cell (EPC) tube formation and migration in conditioned medium from APLN-treated RASFs. We also found significantly higher levels of APLN and Ang1 expression in synovial fluid from RA patients compared with those with osteoarthritis. APLN facilitated Ang1-dependent EPC angiogenesis by inhibiting miR-525-5p synthesis via phospholipase C gamma (PLCγ) and protein kinase C alpha (PKCα) signaling. Importantly, infection with APLN shRNA mitigated EPC angiogenesis, articular swelling, and cartilage erosion in ankle joints of mice with collagen-induced arthritis. APLN is therefore a novel therapeutic target for RA.


Angiopoietin-1/metabolism , Apelin/metabolism , Arthritis, Experimental/metabolism , Arthritis, Rheumatoid/metabolism , Endothelial Progenitor Cells/metabolism , Fibroblasts/metabolism , MicroRNAs/metabolism , Neovascularization, Pathologic , Synoviocytes/metabolism , 3T3 Cells , Angiopoietin-1/genetics , Animals , Apelin/genetics , Arthritis, Experimental/genetics , Arthritis, Experimental/pathology , Arthritis, Experimental/prevention & control , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/pathology , Chick Embryo , Endothelial Progenitor Cells/pathology , Fibroblasts/pathology , Humans , Mice , MicroRNAs/genetics , RNA Interference , Signal Transduction , Synoviocytes/pathology
13.
Life Sci ; 265: 118832, 2021 Jan 15.
Article En | MEDLINE | ID: mdl-33259866

AIMS: Inflammatory macrophages have been proposed as a therapeutic target for joint disorders caused by inflammation. This study aimed to investigate the expression and regulation of coxsackievirus-adenovirus receptor (CAR) in lipopolysaccharide (LPS)-stimulated inflammatory macrophages whereby to evaluate the feasibility of virus-directed enzyme prodrug therapy (VDEPT). MAIN METHODS: Macrophage cell lines (RAW264.7 and J774A.1) and primary macrophage cells derived from rat spleen were used to evaluate the expression of CAR protein or CAR mRNA. Specific inhibitors for TLR4 pathway were used to investigate the regulation of CAR expression. CAR expression in rat joints was documented by immunohistochemistry. Conditionally replicating adenovirus, CRAd-EGFP(PS1217L) or CRAd-NTR(PS1217H6), and non-replicating adenovirus CTL102 were used to transduce genes for enhanced green fluorescent protein (EGFP) or nitroreductase (NTR), respectively. The expression of EGFP, NTR, and the toxicity induced by CB1954 activation were evaluated. KEY FINDINGS: The in vitro experiments revealed that CAR upregulation was mediated through the TLR4/TRIF/IRF3 pathway in LPS-stimulated inflammatory macrophage RAW264.7 and J774A.1 cells. The inflammatory RAW264.7 cells upregulated CAR expression following LPS stimulation, leading to higher infectability, increased NTR expression, and enhanced sensitization to CB1954. In animal experiments, the induction of CAR expression was observed in the CD68-expressing primary macrophages and in the CD68-expressing macrophages within joints following LPS stimulation. SIGNIFICANCE: In conclusion, we report an enhanced CAR expression in inflammatory macrophages in vitro and in vivo through the immune response elicited by LPS. Thus, the TLR4/TRIF/IRF3 pathway of macrophages, when activated, could facilitate the therapeutic application of adenovirus-mediated VDEPT.


Adaptor Proteins, Vesicular Transport/metabolism , Coxsackie and Adenovirus Receptor-Like Membrane Protein/genetics , Immunity, Innate/immunology , Inflammation/pathology , Macrophages/pathology , Adenoviridae/genetics , Animals , Cell Line , Genetic Vectors/administration & dosage , Inflammation/genetics , Inflammation/immunology , Interferon Regulatory Factor-3/metabolism , Lipopolysaccharides , Macrophages/immunology , Male , Mice , RAW 264.7 Cells , Rats , Rats, Sprague-Dawley , Toll-Like Receptor 4/metabolism
14.
Bone Joint Res ; 9(11): 768-777, 2020 Nov.
Article En | MEDLINE | ID: mdl-33135462

AIMS: The material and design of knee components can have a considerable effect on the contact characteristics of the tibial post. This study aimed to analyze the stress distribution on the tibial post when using different grades of polyethylene for the tibial inserts. In addition, the contact properties of fixed-bearing and mobile-bearing inserts were evaluated. METHODS: Three different grades of polyethylene were compared in this study; conventional ultra high molecular weight polyethylene (UHMWPE), highly cross-linked polyethylene (HXLPE), and vitamin E-stabilized polyethylene (VEPE). In addition, tibial baseplates with a fixed-bearing and a mobile-bearing insert were evaluated to understand differences in the contact properties. The inserts were implanted in neutral alignment and with a 10° internal malrotation. The contact stress, von Mises stress, and equivalent plastic strain (PEEQ) on the tibial posts were extracted for comparison. RESULTS: The stress and strain on the tibial post for the three polyethylenes greatly increased when the insert was placed in malrotation, showing a 38% to 56% increase in von Mises stress and a 335% to 434% increase in PEEQ. The VEPE insert had the lowest PEEQ among the three materials. The mobile-bearing design exhibited a lower increase in stress and strain around the tibial posts than the fixed-bearing design. CONCLUSION: Using VEPE for the tibial component potentially eliminates the risk of material permanent deformation. The mobile-bearing insert can help to avoid a dramatic increase in plastic strain around the tibial post in cases of malrotation. The mobility allows the pressure to be distributed on the tibial post and demonstrated lower stresses with all three polyethylenes simulated. Cite this article: Bone Joint Res 2020;9(11):768-777.

15.
Aging (Albany NY) ; 12(10): 9224-9239, 2020 05 18.
Article En | MEDLINE | ID: mdl-32420902

Much data suggests intersecting activities between the adipokine apelin (APLN) and the pathologic processes of obesity and osteoarthritis (OA), with APLN modulating cartilage, synovium, bone, and various immune cell activities. The synovium plays an important role in the pathogenesis of OA. We investigated the crosstalk between APLN, a major OA-related adipokine, and interleukin 1 beta (IL-1ß), a major proinflammatory cytokine, in human OA synovial fibroblasts (OASFs). We showed that APLN stimulated the synthesis of IL-1ß in a concentration- and time-dependent manner, which was mitigated by blockade of the PI3K and ERK pathway. We also showed that APLN inhibited the expression of miRNA-144-3p, which blocks IL-1ß transcription; this suppression activity was reversed via blockade of the PI3K and ERK pathway. Moreover, pathologic changes in OA cartilage were rescued when APLN was silenced by shAPLN transfection both in vitro and in vivo. Our evidence is the first to show that APLN stimulates the expression of IL-1ß by activating the PI3K and ERK pathway and suppressing downstream expression of miRNA-144-3p in OASFs. We also demonstrate that knockdown of APLN expression by shAPLN transfection ameliorated changes in OA cartilage severity. These results shed light on OA pathogenesis and suggest a novel treatment pathway.


Apelin , Class I Phosphatidylinositol 3-Kinases , Interleukin-1beta , MAP Kinase Signaling System , MicroRNAs , Animals , Apelin/genetics , Apelin/metabolism , Apelin/pharmacology , Cells, Cultured , Class I Phosphatidylinositol 3-Kinases/genetics , Class I Phosphatidylinositol 3-Kinases/metabolism , Fibroblasts/drug effects , Fibroblasts/metabolism , Gene Knockdown Techniques , Humans , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , MAP Kinase Signaling System/drug effects , MAP Kinase Signaling System/genetics , MicroRNAs/antagonists & inhibitors , MicroRNAs/genetics , MicroRNAs/metabolism , Osteoarthritis/metabolism , Rats, Sprague-Dawley , Synovial Membrane/cytology
16.
Int J Nanomedicine ; 15: 647-659, 2020.
Article En | MEDLINE | ID: mdl-32099357

BACKGROUND: Graphene and its derivatives have recently gained popularity in the biomedical field. Previous studies have confirmed that both the mechanical strength and wear resistance of graphene-containing polyethylene have been greatly improved. Therefore, it is being considered as an alternative for artificial joint replacement liners. Based on the literature, the wear debris generated from the traditional polymers used for orthopedic liners could lead to particle-induced osteolysis and, consequently, failure of joint replacement. However, the biological response of this novel graphene-based polymer is still unclear. Therefore, the current study aimed to investigate the in vitro and in vivo biological effects of graphene and graphene oxide (GO) particles on bone. MATERIALS AND METHODS: The biological responses of graphene and GO particles were tested via in vitro and murine calvarial in vivo models. In the in vitro model, murine macrophage cells were mixed with particles and hydrogel and printed into two differently designed scaffolds; the induced proinflammatory cytokines were then tested. In the murine in vivo model, the particle size distribution was measured via SEM, and these particles were then administrated in the calvarial area, referring to our established model. A micro-CT and histological analysis were performed to examine the biological effects of the particles on bone health. The data were analyzed via the one-way analysis of variance to determine the differences between the groups. RESULTS: Both graphene and GO induced significantly higher TNF-α and IL-6 secretion compared with the control in the three-dimensional in vitro model. In the murine calvarial in vivo test, the graphene and GO particles increased the bone mass compared with the sham groups in the micro-CT analysis. Bone formation was also observed in the histological analysis. CONCLUSION: In these in vivo and in vitro studies, the graphene and GO wear debris did not seem to induce harmful biological response effect to bone. Bone formation around the skull was observed in the calvarial model instead. Graphene-containing biomaterials could be a suitable new material for application in orthopedic prostheses due to their benefit of eliminating the risk of particle-induce osteolysis.


Graphite/pharmacology , Osteolysis/drug therapy , Skull/drug effects , Animals , Biocompatible Materials/pharmacology , Female , Interleukin-6/metabolism , Macrophages/drug effects , Mice , Mice, Inbred C57BL , Nanoparticles/chemistry , Osteogenesis/drug effects , Osteolysis/pathology , Particle Size , RAW 264.7 Cells , Skull/cytology , Skull/diagnostic imaging , Tissue Scaffolds , Tumor Necrosis Factor-alpha/metabolism , X-Ray Microtomography
17.
Phytomedicine ; 64: 152911, 2019 Nov.
Article En | MEDLINE | ID: mdl-31454653

Background Garcimultiflorone K is a novel polyprenylated polycyclic acylphloroglucinol isolated from the stems of Garcinia multiflora that exhibits promising anti-angiogenic activity in human endothelial progenitor cells (EPCs). Purpose This study sought to determine the underlying anti-angiogenic mechanisms and pharmacological properties of garcimultiflorone K. Methods We examined the anti-angiogenic effects of garcimultiflorone K and its mechanisms of action using in vitro EPC models and in vivo zebrafish embryos. Results EPCs proliferation, migration, differentiation and capillary-like tube formation were effectively and concentration-dependently inhibited by garcimultiflorone K without any signs of cytotoxicity. Our investigations revealed that garcimultiflorone K suppressed EPCs angiogenesis through Akt, mTOR, p70S6K, and eNOS signaling cascades. Notably, garcimultiflorone K dose-dependently impeded angiogenesis in zebrafish embryos. Conclusion Our data demonstrate the anti-angiogneic effects of garcimultiflorone K in both in vitro and in vivo models. Garcimultiflorone K appears to have potential in the treatment of angiogenesis-related diseases.


Angiogenesis Inhibitors/pharmacology , Garcinia/chemistry , Neovascularization, Pathologic/drug therapy , Phloroglucinol/pharmacology , Signal Transduction/drug effects , Angiogenesis Inhibitors/chemistry , Animals , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Endothelial Progenitor Cells/drug effects , Humans , Nitric Oxide Synthase Type III/metabolism , Phloroglucinol/chemistry , Proto-Oncogene Proteins c-akt/metabolism , Ribosomal Protein S6 Kinases, 70-kDa/metabolism , TOR Serine-Threonine Kinases/metabolism , Zebrafish
18.
Clin Biomech (Bristol, Avon) ; 59: 152-158, 2018 11.
Article En | MEDLINE | ID: mdl-30245408

BACKGROUND: Vitamin E-stabilized cross-linked polyethylene has been touted to alleviate the negative effects of oxidation. Although it has demonstrated significant improvements in wear resistance, bio-tribology, and oxidative resistance, little is known about the effect of antioxidants and dosage of cross-linking on the mechanical strength. This study aimed to evaluate the mechanical properties of these novel materials, which are commonly used in orthopedic implants. METHODS: Samples of different polymers were prepared with various levels of cross-linking and with or without vitamin E-stabilization and then tested according to ASTM D695 and D638. The elastoplastic characteristics under compression and tension were compared between the groups. FINDINGS: Vitamin E-stabilized cross-linked polyethylene showed a significant increase in elastic modulus over other groups, with a maximum increase of 26% in compression and 40% in tension when compared to the highly cross-linked group without vitamin E stabilization. The elastoplastic behavior under compression differed to that in tension for all polymers, demonstrating the anisotropic characteristics of these polymers. INTERPRETATION: The lower mechanical strength of highly cross-linked polyethylene has been a complication with the use of this polymer in orthopedic liners. This current study suggests that vitamin E-stabilized cross-linked polyethylene could be a suitable alternative material for knee implants because of its improved strength in resisting external forces.


Antioxidants/chemistry , Elastic Modulus , Materials Testing , Polyethylene/chemistry , Prostheses and Implants , Vitamin E/chemistry , Humans , Prosthesis Design , Stress, Mechanical , Tensile Strength
19.
Knee Surg Sports Traumatol Arthrosc ; 25(1): 263-271, 2017 Jan.
Article En | MEDLINE | ID: mdl-25539687

PURPOSE: Whether to resurface the patella in knee replacement remains a controversial issue. The geometrical design of the trochlear groove in the femoral component could play an important role in determining the stress distribution on the patellofemoral joint, but this has not been sufficiently reported on. This study attempted to determine the effect of implant design on contact mechanics by means of a finite element method. METHODS: Two designs, an anatomical V-shape design (VSD) and a dome-shape design (DSD), for the anterior trochlear surface in a contemporary femoral component were chosen for examining the contact characteristics. The use and absence of patella resurfacing was simulated. The stress and strain distribution on the patellar bone and the polyethylene component were calculated for comparison. RESULTS: Without patellar resurfacing, the maximal compressive strain in the patellar bone in the VSD model was about 20 % lower than the DSD model. On the other hand, with resurfacing, the maximal strain for the VSD model was 13.3 % greater than for DSD. Uneven stress distribution at the bone-implant interface was also noted for the two designs. CONCLUSION: The femoral component with a V-shape trochlear groove reduced the compressive strain on the unresurfaced patella. If resurfacing the patella, the femoral component with a curved domed-shape design might reduce the strain in the remaining patellar bone. Uneven stress could occur at the bone-implant interface, so design modifications for improving fixation strength and medialization of the patellar button would be helpful in reducing the risk of peg fracture or loosening. LEVEL OF EVIDENCE: III.


Arthroplasty, Replacement, Knee/methods , Knee Prosthesis , Patella/surgery , Patellofemoral Joint/surgery , Prosthesis Design , Weight-Bearing/physiology , Case-Control Studies , Finite Element Analysis , Humans , Models, Anatomic , Patellofemoral Joint/physiopathology , Polyethylene , Stress, Mechanical
20.
J Adv Nurs ; 72(8): 1825-37, 2016 Aug.
Article En | MEDLINE | ID: mdl-27029950

AIM: The aim of this study was to explore the effects of a self-management intervention for middle-aged adults with knee osteoarthritis. BACKGROUND: Knee osteoarthritis is a common cause of lower limb disability in middle-aged and older adults. Use of self-management interventions that apply the self-regulation theory have not been reported for patients with knee osteoarthritis. DESIGN: A quasi-experimental design was applied. METHODS: Knee osteoarthritis patients were recruited from two medical centres in northern Taiwan by convenience sampling between July 2013-May 2014. We developed a self-management intervention programme for knee osteoarthritis; participants began an individualized programme 4 weeks after recruitment. Effectiveness of the intervention was evaluated using the Knee Injury and Osteoarthritis Outcome Score, Health Care Questionnaire and the Short-Form Health Survey. A generalized estimating equation compared assessment scores for 105 participants after the intervention (10 and 18 weeks) with scores at 4 weeks. RESULTS: Knee symptoms and physical function scores significantly improved and quality-of-life scores significantly increased while body mass index, unplanned medical consultations and doses of pain medication significantly decreased at 10 and 18 weeks compared with 4 weeks. After adjusting for the effect of time- and significant-related factors, knee symptoms and physical function, body mass index and quality of life significantly improved at 10 and 18 weeks compared with 4 weeks. CONCLUSIONS: The self-management intervention based on self-regulation theory, improved participants' symptoms and functions of knee osteoarthritis, overall health and quality of life. Offering self-management interventions in clinical practice can be beneficial for patients with knee osteoarthritis.


Osteoarthritis, Knee/nursing , Self-Management , Adult , Female , Humans , Male , Middle Aged , Pain , Quality of Life , Taiwan
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