scholarly journals Toddalolactone Protects Against Osteoarthritis by Ameliorating Chondrocyte Inflammation and Suppressing Osteoclastogenesis

2021 ◽  
Author(s):  
Yiming Xu ◽  
Song Xue ◽  
Tian Zhang ◽  
Xinmeng Jin ◽  
Cong Wang ◽  
...  
Keyword(s):  
Cruciate Ligament ◽  
Osteoclast Differentiation ◽  
Joint Disease ◽  
Marker Genes ◽  
Mapk Signalling ◽  
Cartilage Erosion ◽  
Anterior Cruciate ◽  
Toddalia Asiatica

Abstract Background: Osteoarthritis (OA) is widely recognized as the most common chronic joint disease accompanied by progressive cartilage and subchondral bone damage. Toddalolactone (TOD), a natural compound extracted from Toddalia asiatica (L.) Lam., has been widely used in the treatment of stroke, rheumatoid arthritis, and oedema. Nevertheless, what TOD acts as in the pathogenesis and progression of OA hasn’t been reported. In this investigation, we have aimed to determine how TOD affects OA in vitro and in vivo.Methods: LPS (10μg/ml) was employed to induce chondrocyte inflammation or RANKL to induce osteoclast differentiation in bone marrow derived macrophages (BMMs); Meanwhile, the effects of TOD on chondrocyte inflammation and osteoclast differentiation were evaluated. Anterior cruciate ligament transection (ACLT) was performed to develop an OA animal model and study the effects of TOD.Results: We found that TOD inhibited the expression of inflammatory and catabolic mediators ( IL-6, IL-8, TNF-α, MMP2, MMP9, and MMP13) in LPS-treated chondrocytes in vitro. Furthermore, TOD was proven to inhibit RANKL-induced-osteoclastogenesis and inhibit the expression of marker genes (NFATc1 and c-fos). Our data also confirmed that TOD suppressed the destruction of articular cartilage and osteoclastogenesis by inhibiting the activation of the NF-κB and MAPK signalling pathways. In the ACLT mouse model, we found that TOD attenuated the ACLT-induced cartilage erosion and inhibited bone resorption.Conclusions: These results showed that TOD can be adopted as a potential therapeutic agent for OA.

In-Vivo Force Estimation of the Anterior Cruciate Ligament

2009 ◽  
Author(s):  
Ali Hosseini ◽  
Thomas J. Gill ◽  
Guoan Li
Keyword(s):  
Anterior Cruciate Ligament ◽  
Cruciate Ligament ◽  
Acl Injury ◽  
Force Estimation ◽  
Non Invasive ◽  
Injury Mechanisms ◽  
Invasive Method ◽  
Anterior Cruciate

The knowledge of in-vivo ACL forces is instrumental for understanding ACL injury mechanisms and for improving surgical ACL reconstruction techniques. Several in-vitro investigations have measured ACL forces in response to various loads applied to the knee. However, in-vivo ACL forces in response to controlled loading are still unknown. The objective of this study was to estimate the force of healthy ACL as well as the possible upper bound of ACL forces under an increasing axial tibial loading in living subjects using a non-invasive method.

REGENERATION OF ANTERIOR CRUCIATE LIGAMENT WITH SILK-BASED SCAFFOLD IN PORCINE MODEL

2015 ◽  
Vol 15 (01) ◽  
pp. 1550006 ◽  
Author(s):  
ZHENG LI ◽  
JIANKANG HE ◽  
XIANG LI ◽  
WEIGUO BIAN ◽  
WENYOU ZHANG ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Anterior Cruciate Ligament ◽  
Porcine Model ◽  
Cruciate Ligament ◽  
Silk Fibers ◽  
Bone Interface ◽  
Anterior Cruciate ◽  
Large Animals

Silk was widely investigated as a promising scaffold material in ligament tissue engineering. Although a variety of silk scaffolds were developed for the regeneration of anterior cruciate ligament (ACL) in vitro and in vivo, more investigations should be performed in large animals to translate these findings into clinical applications. The aim of this study is to evaluate the feasibility of using silk-based ACL scaffolds to regenerate damaged ACLs in porcine model. The microstructural organization, tissue regeneration as well as ligament-bone interface of silk implants were evaluated with scanning electron microscopy, micro-computerized tomography, histological and immunohistochemical staining at three and six months postoperatively. The results demonstrated that silk fibers in the ACL scaffolds organized in parallel similar with collagen fibers in native ligaments, which facilitated and guided the penetration of newly regenerated tissue into the pores among silk fibers. Collagen production especially collagen I in silk implants significantly increased from three to six months, and was gradually close to the level of native ligaments. At implant-bone interface, indirect ligament-bone insertion was observed at three months and substantial Sharpey's fibers formed at six months. The results indicated that the silk-based ACL scaffold provides a promising tissue engineering approach for ACL regeneration.

Silk fibroin coating through EDC/NHS crosslink is an effective method to promote graft remodeling of a polyethylene terephthalate artificial ligament

2019 ◽  
Vol 33 (10) ◽  
pp. 1407-1414 ◽  
Author(s):  
Jiangyu Cai ◽  
Li Zhang ◽  
Jun Chen ◽  
Shiyi Chen
Keyword(s):  
Anterior Cruciate Ligament ◽  
Anterior Cruciate Ligament Reconstruction ◽  
Polyethylene Terephthalate ◽  
Silk Fibroin ◽  
Ligament Reconstruction ◽  
Cruciate Ligament ◽  
Cruciate Ligament Reconstruction ◽  
Anterior Cruciate

Anterior cruciate ligament reconstruction using polyethylene terephthalate artificial ligaments is one of the research hotspots in sports medicine but it is still challenging to achieve biological healing. The purpose of this study was to modify polyethylene terephthalate ligament with silk fibroin through ethyl-3–(3-dimethylaminopropyl)carbodiimide (EDC)/N-hydroxysuccinimide (NHS) crosslink and to investigate the performance of graft remodeling in vitro and in vivo. After silk fibroin coating, changes in the surface properties of ligament were characterized by scanning electron microscopy, attenuated total reflectance-Fourier transform infrared spectroscopy and water contact angle measurements. The compatibility of polyethylene terephthalate ligament with silk fibroin coating was investigated in vitro. The results showed the silk fibroin coating significantly improved adhesion, proliferation and extracellular matrix secretion of fibroblast cells. Moreover, a rabbit anterior cruciate ligament reconstruction model was established to evaluate the effect of ligament with silk fibroin coating in vivo. The gross observation and histological results showed that the silk fibroin coating significantly inhibited inflammation response and promoted new tissue regeneration with fusiform cells infiltration in and around the graft. Furthermore, the expressions of collagen I protein and mRNA in the silk fibroin-coated polyethylene terephthalate group were much higher than those in the control group according to the immunohistochemical and real-time polymerase chain reaction results. Therefore, silk fibroin coating through EDC/NHS crosslink promotes the biocompatibility and remodeling process of polyethylene terephthalate artificial ligament in vitro and in vivo. It can be considered as a potential solution to the problem of poor remodeling of artificial ligaments after anterior cruciate ligament reconstruction in the clinical applications.

Does Graft Construct Lengthening at the Fixations Cause an Increase in Anterior Laxity Following Anterior Cruciate Ligament Reconstruction in vivo?

2010 ◽  
Vol 132 (8) ◽  
Author(s):  
Conrad K. Smith ◽  
M. L. Hull ◽  
S. M. Howell
Keyword(s):  
Anterior Cruciate Ligament ◽  
Cruciate Ligament ◽  
Bone Tunnel ◽  
Anterior Cruciate Ligament Graft ◽  
Potential Increase ◽  
Anterior Laxity ◽  
Fresh Frozen ◽  
Anterior Cruciate

A millimeter-for-millimeter relation between an increase in length of an anterior cruciate ligament graft construct and an increase in anterior laxity has been demonstrated in multiple in vitro studies. Based on this relation, a 3 mm increase in length of the graft construct following surgery could manifest as a 3 mm increase in anterior laxity in vivo, which is considered clinically unstable. Hence, the two primary objectives were to determine whether the millimeter-for-millimeter relation exists in vivo for slippage-resistant fixation of a soft-tissue graft and, if it does not exist, then to what extent the increase in stiffness caused by biologic healing of the graft to the bone tunnel offsets the potential increase in anterior laxity resulting from lengthening at the sites of fixation. Sixteen subjects were treated with a fresh-frozen, nonirradiated, nonchemically processed tibialis allograft. Tantalum markers were injected into the graft, fixation devices, and bones. On the day of surgery and at 1, 2, 3, and 4 months, Roentgen stereophotogrammetric analysis was used to compute anterior laxity at 150 N of anterior force and the total slippage from both sites of fixation. A simple linear regression was performed to determine whether the millimeter-for-millimeter relation existed and a springs-in-series model of the graft construct was used to determine the extent to which the increase in stiffness caused by biological healing of the graft to the bone tunnel offset the increase in anterior laxity resulting from lengthening at the sites of fixation. There was no correlation between lengthening at the sites of fixation and the increase in anterior laxity at 1 month (R2=0.0, slope=0.2). Also, the increase in stiffness of the graft construct caused by biologic healing of the graft to the bone tunnel offset 0.7 mm of the 1.5 mm potential increase in anterior laxity resulting from lengthening at the sites of fixation. This relatively large offset of nearly 50% occurred because lengthening at the sites of fixation was small.

scholarly journals α2-Macroglobulin-Rich Serum As a Master Inhibitor of Inflammatory Factors Attenuates Cartilage Degeneration in a Mini Pig Model of Osteoarthritis Induced By “Idealized” Anterior Cruciate Ligament Reconstruction

2021 ◽  
Author(s):  
Ruipeng Zhao ◽  
Xiaochun Wei ◽  
Chengming Zhang ◽  
Hongru Wu ◽  
Chuan Xiang ◽  
...  
Keyword(s):  
Anterior Cruciate Ligament ◽  
Cruciate Ligament ◽  
Cartilage Degeneration ◽  
Mature Female ◽  
Inflammatory Factors ◽  
Post Surgery ◽  
Α2 Macroglobulin ◽  
Anterior Cruciate

Abstract Background: α2-Macroglobulin (α2M) is important for chondral protection in post-traumatic osteoarthritis (PTOA). However, its injection into xenogeneic joint cavities has safety hazards, limiting clinical applications. Exploring serum α2M-enriching strategies and the therapeutic effect and mechanism of α2M-rich serum (α2MRS) autologous joint injection to treat PTOA has significant value.Methods: A unique filtration process was used to concentrate α2M from serum. Human osteoarthritic chondrocytes induced with interleukin (IL)-1β were used to evaluate catabolic enzymes, cell proliferation, apoptosis, and gene expression 24h after α2MRS treatment. Eighteen mature female mini pigs were randomized to three groups, sham (n = 6), “idealized” anterior cruciate ligament autograft reconstruction (IACL-R) (n = 6), and IACL-R+α2MRS (n = 6). Expression of inflammatory factors in the synovial fluid (SF) was measured using Luminex assays. Gait features were recorded using the Tekscan Walkway system. The extent of PTOA progression was evaluated using imaging, real-time PCR , and histology 3 months post-surgery.Results: The α2M concentration in α2MRS was higher than that in human and mini pig serum, respectively. In vitro, α2MRS significantly promoted human chondrocyte proliferation (p < 0.001) and reduced apoptosis (p < 0.001) and chondrocyte catabolic cytokine gene transcription (p < 0.001) and secretion (p < 0.001). In vivo, SF concentrations of all tested inflammatory factors were significantly lower in the IACL-R+α2MRS group than in the IACL-R group (p < 0.001). All gait parameters in the IACL-R+α2MRS group returned to normal significantly early compared to those in the IACL-R group (p < 0.05). Imaging , histology, and biochemistry data showed that cartilage degeneration in the IACL-R+α2MRS group was significantly diminished relative to that in the IACL-R group (p < 0.001).Conclusion: Injecting α2MRS into the joint cavity after IACL-R can significantly delay articular cartilage degeneration.

scholarly journals Inhibition of Rac1 activity by controlled release of NSC23766 from chitosan microspheres effectively ameliorates osteoarthritis development in vivo

2013 ◽  
Vol 74 (1) ◽  
pp. 285-293 ◽  
Author(s):  
Shouan Zhu ◽  
Ping Lu ◽  
Huanhuan Liu ◽  
Pengfei Chen ◽  
Yan Wu ◽  
...  
Keyword(s):  
Controlled Release ◽  
Cruciate Ligament ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Activity Assay ◽  
Chondrocyte Hypertrophy ◽  
Chitosan Microspheres ◽  
Rac1 Activity

BackgroundOsteoarthritis (OA) is a degenerative joint disease characterised by cartilage degradation and chondrocyte hypertrophy. A recent study showed that Rac1 promoted expression of MMP13 and chondrocyte hypertrophy within the growth plate. These findings warrant further investigations on the roles of Rac1 in OA development and therapy in animal models.ObjectiveTo investigate the role and mechanistic pathway of Rac1 involvement in pathological changes of OA chondrocytes in vitro and OA development in vivo, as well as to develop a strategy of modulating Rac1 activity for OA treatment.Material and methodsOA and normal cartilage from human or mice were used for immunohistochemical study and Rac1 activity assay. Chondrocytes treated with IL1β and the untreated control were subjected to the Rac1 activity assay. Chondrocytes transfected with CA-Rac1, DN-Rac1 or GFP were cultured under conditions for inducing calcification. To evaluate the effect of Rac1 in OA development, an OA model was created by anterior cruciate ligament transection in mice. CA-Rac1, DN-Rac1 and GFP lentivirus, or NSC23766, were injected intra-articularly. Joints were subjected to histological analysis.ResultsIt was found that there is aberrant Rac1 activation in human OA cartilage. Rac1 activity could also be elevated by IL1β. Additionally, activated Rac1 promoted expression of MMP13, ADAMTS-5 and COLX by chondrocytes, partially through the β-catenin pathway. Moreover, activation of Rac1 in knee joints by CA-Rac1 lentivirus accelerated OA progression, while inhibition of Rac1 activity by DN-Rac1 lentivirus or Rac1 inhibitor NSC23766 delayed OA development. Therefore, we developed a strategy of controlled release of NSC23766 from chitosan microspheres to OA joints, which effectively protected cartilage from destruction.ConclusionsThese findings demonstrated that Rac1 activity is implicated in OA development. Also, controlled release of Rac1 inhibitor is a promising strategy for OA treatment.

The Tissue Engineering Approach to Ligament Reconstruction

1993 ◽  
Vol 331 ◽  
Author(s):  
Michael G. Dunn ◽  
J. B. Liesch ◽  
M. L. Tiku ◽  
S. H. Maxian ◽  
J. P. Zawadsky
Keyword(s):  
Acl Reconstruction ◽  
Patellar Tendon ◽  
Cruciate Ligament ◽  
Collagen Scaffold ◽  
In Vivo Studies ◽  
Collagen Scaffolds ◽  
Tissue Engineering Approach ◽  
Anterior Cruciate

AbstractPrevious studies in our laboratory showed that acellular collagen scaffold implants induce tissue ingrowth and perform similar to autografts following reconstruction of rabbit Achilles tendon or anterior cruciate ligament (ACL). We chronologically review these and related studies, and report preliminary development of fibroblast-seeded collagen scaffolds potentially useful for ACL reconstruction. The ‘healing potential’ of fibroblasts was measured within collagen scaffolds in vitro, as a function of fibroblast source. Aligned collagen scaffolds were seeded with fibroblasts from rabbit ACL, synovium, patellar tendon, or skin. Fibroblast viability, adherence, spreading, proliferation, and protein and collagen deposition were measured on collagen scaffolds. The fibroblasts attached to the scaffolds, and spread along the long axis of the collagen fibers. ACL fibroblasts adhered better than other fibroblast types; however, the ACL fibroblasts proliferated at the slowest rate. Patellar tendon fibroblasts proliferated at the most rapid rate. All four of the fibroblast types secreted protein and collagen within the collagen scaffolds.Preliminary in vivo studies suggest that fibroblasts seeded onto collagen scaffolds can remain viable following reimplantation into the donor rabbit. Ongoing studies will elucidate the role of autogenous seeded fibroblasts in neoligament formation/remodeling. These ‘ligament analogs’ are potentially useful for clinical ACL reconstruction: fibroblasts would be obtained from biopsy, cultured, seeded onto a collagen scaffold, and implanted as an ACL substitute into the same patient.

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