scholarly journals Phytochemicals Mediate Autophagy Against Osteoarthritis by Maintaining Cartilage Homeostasis

2021 ◽  
Vol 12 ◽  
Author(s):  
Zheng Tian ◽  
Xinan Zhang ◽  
Mingli Sun
Keyword(s):  
Signaling Pathways ◽  
Therapeutic Option ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Chondrocyte Apoptosis ◽  
Protective Mechanism ◽  
Inflammatory Factor ◽  
Cartilage Homeostasis ◽  
Pharmacological Tests

Osteoarthritis (OA) is a common degenerative joint disease and is a leading cause of disability and reduced quality of life worldwide. There are currently no clinical treatments that can stop or slow down OA. Drugs have pain-relieving effects, but they do not slow down the course of OA and their long-term use can lead to serious side effects. Therefore, safe and clinically appropriate long-term treatments for OA are urgently needed. Autophagy is an intracellular protective mechanism, and targeting autophagy-related pathways has been found to prevent and treat various diseases. Attenuation of the autophagic pathway has now been found to disrupt cartilage homeostasis and plays an important role in the development of OA. Therefore, modulation of autophagic signaling pathways mediating cartilage homeostasis has been considered as a potential therapeutic option for OA. Phytochemicals are active ingredients from plants that have recently been found to reduce inflammatory factor levels in cartilage as well as attenuate chondrocyte apoptosis by modulating autophagy-related signaling pathways, which are not only widely available but also have the potential to alleviate the symptoms of OA. We reviewed preclinical studies and clinical studies of phytochemicals mediating autophagy to regulate cartilage homeostasis for the treatment of OA. The results suggest that phytochemicals derived from plant extracts can target relevant autophagic pathways as complementary and alternative agents for the treatment of OA if subjected to rigorous clinical trials and pharmacological tests.

scholarly journals Induction of WNT16 via Peptide-mRNA Nanoparticle-Based Delivery Maintains Cartilage Homeostasis

Pharmaceutics ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 73
Author(s):  
Huimin Yan ◽  
Ying Hu ◽  
Antonina Akk ◽  
Muhammad Farooq Rai ◽  
Hua Pan ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Treatment Options ◽  
Cartilage Explants ◽  
Joint Disease ◽  
Chondrocyte Apoptosis ◽  
Proof Of Concept ◽  
Human Cartilage ◽  
Cartilage Homeostasis ◽  
Wide Range ◽  
Significant Disability

Osteoarthritis (OA) is a progressive joint disease that causes significant disability and pain and for which there are limited treatment options. We posit that delivery of anabolic factors that protect and maintain cartilage homeostasis will halt or retard OA progression. We employ a peptide-based nanoplatform to deliver Wingless and the name Int-1 (WNT) 16 messenger RNA (mRNA) to human cartilage explants. The peptide forms a self-assembled nanocomplex of approximately 65 nm in size when incubated with WNT16 mRNA. The complex is further stabilized with hyaluronic acid (HA) for enhanced cellular uptake. Delivery of peptide-WNT16 mRNA nanocomplex to human cartilage explants antagonizes canonical β-catenin/WNT3a signaling, leading to increased lubricin production and decreased chondrocyte apoptosis. This is a proof-of-concept study showing that mRNA can be efficiently delivered to articular cartilage, an avascular tissue that is poorly accessible even when drugs are intra-articularly (IA) administered. The ability to accommodate a wide range of oligonucleotides suggests that this platform may find use in a broad range of clinical applications.

Owner Perceptions of Long-Term Systemic Use of Subcutaneous Administration of Polysulfated Glycosaminoglycan

2021 ◽  
Author(s):  
Gabriella Varcoe ◽  
Julia Tomlinson ◽  
Jane Manfredi
Keyword(s):  
Adverse Event ◽  
Adverse Events ◽  
Gastrointestinal Symptoms ◽  
Subcutaneous Administration ◽  
Degenerative Joint Disease ◽  
Severe Adverse Event ◽  
Joint Disease ◽  
Disease Modifying ◽  
Rehabilitation Clinic

ABSTRACT Polysulfated glycosaminoglycan (PSGAG) is a slow-acting disease-modifying agent used to treat degenerative joint disease. Although labeled for intramuscular use, it is commonly given by owners via a subcutaneous (SC) route. There is little information on adverse events related to SC administration or what other therapies are used concurrently with PSGAG. We hypothesized that SC PSGAG is perceived by owners as having minimal adverse events and that it would most often be given with other therapies. Owners (n = 378) were surveyed about their perceptions regarding SC PSGAG prescribed to dogs at one veterinary rehabilitation clinic. Complete surveys were provided for 69 dogs (two owners had multiple dogs). Overall, 13/69 (18.8%) dogs had an adverse event reported during the use of PSGAG. Most events were considered minor (stomach upset, loose stool, pain at injection site, fear) and did not lead to discontinuation of PSGAG. One dog experienced a moderate adverse event (persistent gastrointestinal symptoms) and one a severe adverse event (thrombocytopenia, bruising), which resolved after discontinuing PSGAG. PSGAG is most commonly administered along with other medications and rehabilitation therapies. The present study demonstrates that SC administration of PSGAG is well tolerated in most of the dogs, with primarily mild, self-resolving adverse events.

scholarly journals Intermediate to Long Term Clinical and Radiographic Outcomes of Triple Arthrodesis: A 422 Case Retrospective Review

2019 ◽  
Vol 4 (4) ◽  
pp. 2473011419S0025
Author(s):  
Jesse King ◽  
Karl Henrikson ◽  
Thomas Harper ◽  
Mike Anderson ◽  
Chris Stauch ◽  
...  
Keyword(s):  
Infection Rate ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Triple Arthrodesis ◽  
Non Union ◽  
Radiographic Outcomes ◽  
Diabetic Status ◽  
Radiographic Data

Category: Ankle Arthritis, Hindfoot Introduction/Purpose: Triple arthrodesis is a commonly performed surgical treatment for hindfoot arthritis and deformity. No study has clearly delineated correlates of both clinical and radiographic outcomes in a sample size this large. The purpose of this study is to explore predictive and demographic outcome measures with long-term followup after triple arthrodesis. Methods: With IRB approval, an institutional radiology database was queried for patients undergoing triple arthrodesis between 2004 and 2016, by a single surgeon at a single institution. A total of 465 cases were identified. Pre- and post-operative clinical and radiographic data was collected retrospectively. Demographic and predictive data included: age, Body Mass Index (BMI), American Society of Anesthesiologists Score (ASA), Charleston Comorbidity Index (CCI), diabetic status, osteoporosis, hypothyroidism, and neuromuscular disease status. Clinical outcomes including infection rate, reoperation rate and clinical nonunion were recorded. Unintended return to the operating room defined clinical failure. Radiographic data including non-union rate, pre- and post- operative ankle degenerative joint disease was also recorded. Statistical analysis was then performed to evaluate the relationship between predictive measures and various outcomes including reoperation, infection, and non-union rates. 23 cases were lost to follow-up. Results: A total of 442 feet (397 patients) were analyzed. The average age was 54 years (14 to 85) with the majority of cases being female (60%). Average follow up was 593 days (40 to 4079). Overall failure rate was 13.7% with clinical nonunion rate of 4.5%. Infection rate was 5.9%. Mortality rate was 0% at 2 years post-operatively. Predictors of failure included: increased BMI, elevated ASA, history of diabetes, underlying neuromuscular disorder (Figure 1). We found no significant difference between pre and post-operative degenerative joint disease rates in the midfoot (9.4%, 12.5%) and ankle (11.7%,13.7%), respectively. Conclusion: Triple arthrodesis is a highly effective procedure for treating hindfoot arthritis. Certain predictive measures including BMI, ASA score, diabetic status and underlying neuromuscular disorders significantly correlate with radiographic union. Additionally, diabetic status significantly correlates with infection status postoperatively. An understanding of these predictive measures may help surgeons in their preoperative planning to improve their clinical and radiographic success rates.

scholarly journals Bax Targeted by miR-29a Regulates Chondrocyte Apoptosis in Osteoarthritis

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Guiqiang Miao ◽  
Xuehui Zang ◽  
Huige Hou ◽  
Hui Sun ◽  
Lihui Wang ◽  
...  
Keyword(s):  
Cartilage Degeneration ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Luciferase Reporter ◽  
Chondrocyte Apoptosis ◽  
Reporter Assay ◽  
Proapoptotic Protein ◽  
Regulation Mechanisms ◽  
Direct Target

Osteoarthritis (OA) is a chronic degenerative joint disease, where chondrocyte apoptosis is responsible for cartilage degeneration. Bax is a well-known proapoptotic protein of the Bcl-2 family, involved in a large number of physiological and pathological processes. However, the regulation mechanisms of Bax underlying chondrocyte apoptosis in OA remain unknown. In the present study, we determined the role of Bax in human OA and chondrocyte apoptosis. The results showed that Bax was upregulated in chondrocytes from the articular cartilage of OA patients and in cultured chondrocyte-like ATDC5 cells treated by IL-1β. Bax was identified to be the direct target of miR-29a by luciferase reporter assay and by western blotting. Inhibition of miR-29a by the mimics protested and overexpression by miR-29a inhibitors aggravated ATDC5 apoptosis induced by IL-1β. These data reveal that miR-29a/Bax axis plays an important role in regulating chondrocyte apoptosis and suggest that targeting the proapoptotic protein Bax and increasing expression levels of miR-29a emerge as potential approach for protection against the development of OA.

scholarly journals Chondroprotective Activity ofMurraya exoticathrough Inhibitingβ-Catenin Signaling Pathway

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Longhuo Wu ◽  
Haiqing Liu ◽  
Rui Zhang ◽  
Linfu Li ◽  
Jialin Li ◽  
...  
Keyword(s):  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Chondrocyte Apoptosis ◽  
Dependent Manner ◽  
Chain Reaction ◽  
Protein Expressions ◽  
Murraya Exotica ◽  
Oa Chondrocytes ◽  
Polymerase Chain ◽  
Dose Dependent

Osteoarthritis (OA) is a degenerative joint disease that affects millions of people. Currently, there is no effective drug treatment for it. The purpose of this study is to investigate the chondroprotective effects ofMurraya exotica(L.) on OA. The rat OA models were duplicated to prepare for separating OA chondrocytes, synovial fluid (SF), and serum containingM. exotica(50 mg/kg, 100 mg/kg, and 200 mg/kg),M. exoticashowed the activity of decreasing the contents of TNF-αand IL-1βin SF and the chondrocyte apoptosis in a dose-dependent manner. To investigate the probable mechanism, quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used to determine gene expression and protein profiles, respectively. The results reveal thatM. exoticacan downregulate mRNA and protein expressions ofβ-catenin and COX-2 and reporter activity significantly. Conclusively,M. exoticaexhibits antiapoptotic chondroprotective activity probably through inhibitingβ-catenin signaling.

Chondroitin - application in the treatment of degenerative joint disease

2016 ◽  
Vol 18 (6) ◽  
pp. 621-628 ◽  
Author(s):  
Wiesław Tomaszewski
Keyword(s):  
Molecular Level ◽  
Proteolytic Enzymes ◽  
Chondroitin Sulphate ◽  
Cartilage Degradation ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Chondrocyte Apoptosis ◽  
Structural Elements ◽  
Acid Biosynthesis ◽  
Physiological Processes

Chondroitin is an organic compound, belonging to the group of glycosaminoglycans. In the treatment of degenerative joint disease, aka osteoarthritis, chondroitin sulphate is applied as a medicine or a dietary supplement. The biological importance of chondroitin sulphate has been already largely determined. The newest data on glycobiology research suggest that proteoglycans, as well as their complex polysaccharide macroparticles not only are the structural elements, but also they participate in multiple metabolic processes at a molecular level as well as in the physiological processes, regulating this type of mechanisms. The preparations applied in the treatment of degenerative joint disease, containing chondroitin sulphate, are attributed numerous therapeutic and chondroprotective properties including stabilizing synthesis processes and cartilage degradation through stimulation and inhibition of chondrocyte apoptosis (production of the elements of the intracellular substance and osteocyte stimulation), an increased proteoglycan and hyaluronic acid biosynthesis, inhibition of the activity of proteolytic enzymes and hyaluronidase, reduction of inflammatory mediators (prostaglandins and leukotrienes) and a decreased collagen II degradation. Based on the results of the multidirectional research available in the newest source literature, the analysis of the therapeutic efficacy and safety of chondroitin application in the treatment of degenerative joint disease was conducted.

Clinical Evaluation and Long-Term Follow-Up of Dogs Having Coronoidectomy for Elbow Incongruity

2003 ◽  
Vol 39 (5) ◽  
pp. 473-478 ◽  
Author(s):  
Margaret Puccio ◽  
Dominic J. Marino ◽  
Joseph D. Stefanacci ◽  
Brian McKenna
Keyword(s):  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Disease Entity ◽  
Radiographic Findings ◽  
Clinical Presentations ◽  
Long Term Follow Up ◽  
The Mean ◽  
Joint Incongruity

A retrospective study was performed describing the clinical presentations, radiographic findings, and surgical outcomes of 17 dogs (18 elbows) following medial coronoidectomy for the treatment of elbow joint incongruity as a sole disease entity. Complete resolution of lameness was achieved in 100% of the cases. The mean radiographic arthrosis grade progressed in 70% of the cases. Results of this study indicate that resolution of clinical lameness may be achieved with medial coronoidectomy in dogs with elbow incongruity; however, progression of degenerative joint disease with unknown, long-term clinical significance can be expected after surgery.

Role of Arthroscopy in Ankle Degenerative Joint Disease: Long Term Retrospective Outcome (SS-48)

2013 ◽  
Vol 29 (6) ◽  
pp. e23-e24
Author(s):  
Francesco Allegra ◽  
Fabio Cerza ◽  
Emanuele Delianni ◽  
Stefano El Boustany ◽  
Roberto Zannoni
Keyword(s):  
Degenerative Joint Disease ◽  
Joint Disease

Traumatic Coxofemoral Luxation in Dysplastic Dogs Managed with a Triple Pelvic Osteotomy: Results in four Dogs

1997 ◽  
Vol 10 (03) ◽  
pp. 136-140 ◽  
Author(s):  
D. D. Lewis ◽  
S. C. Kerwin ◽  
S. T. Murphy
Keyword(s):  
Femoral Head ◽  
Hip Dysplasia ◽  
External Rotation ◽  
Pelvic Osteotomy ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Contralateral Limb ◽  
Norberg Angle

SummaryTriple pelvic osteotomy (TPO) was used in the treatment for traumatic coxofemoral luxations in four adult, large breed dogs with hip dysplasia. Initial closed reductions failed in three and one dog had an initial closed reduction and subsequent open reduction of the coxofemoral luxation that failed. Hip dysplasia was thought to be a prominent factor contributing to the reluxation. TPO successfully maintained reduction of the coxofemoral luxation in all of the dogs. An increase in dorsal acetabular coverage of the femoral head following TPO was demonstrated by an increased Norberg angle. The improved congruency was thought to maintain reduction of the femoral head in the acetabulum and decrease stresses on the joint capsule, allowing healing to occur. Long-term (median: 343, mean ± SD: 406 ± 226 days follow-up) function of the affected limb was comparable to the contralateral limb. Three of the four dogs did not have radiographic progression of coxofemoral degenerative joint disease of the affected joint and differences in the progression of degenerative joint disease were not evident between the affected and the contralateral coxofemoral joint. A decrease in abduction and external rotation and an increase in internal rotation following TPO was noted in the affected coxofemoral joint. Our results establish the utility of this procedure in dysplastic dogs with traumatic coxofemoral luxations.Triple pelvic osteotomy used in the treatment for traumatic coxofemoral luxation in four adult, large breed dogs with hip dysplasia successfully maintained reduction and resulted in satisfactory limb function in all patients.

Owner Perceptions of Long-Term Systemic Use of Subcutaneous Administration of Polysulfated Glycosaminoglycan

2021 ◽  
Vol 57 (5) ◽  
pp. 205-211
Author(s):  
Gabriella Varcoe ◽  
Julia Tomlinson ◽  
Jane Manfredi
Keyword(s):  
Adverse Event ◽  
Adverse Events ◽  
Gastrointestinal Symptoms ◽  
Subcutaneous Administration ◽  
Degenerative Joint Disease ◽  
Severe Adverse Event ◽  
Joint Disease ◽  
Disease Modifying ◽  
Rehabilitation Clinic

ABSTRACT Polysulfated glycosaminoglycan (PSGAG) is a slow-acting disease-modifying agent used to treat degenerative joint disease. Although labeled for intramuscular use, it is commonly given by owners via a subcutaneous (SC) route. There is little information on adverse events related to SC administration or what other therapies are used concurrently with PSGAG. We hypothesized that SC PSGAG is perceived by owners as having minimal adverse events and that it would most often be given with other therapies. Owners (n = 378) were surveyed about their perceptions regarding SC PSGAG prescribed to dogs at one veterinary rehabilitation clinic. Complete surveys were provided for 69 dogs (two owners had multiple dogs). Overall, 13/69 (18.8%) dogs had an adverse event reported during the use of PSGAG. Most events were considered minor (stomach upset, loose stool, pain at injection site, fear) and did not lead to discontinuation of PSGAG. One dog experienced a moderate adverse event (persistent gastrointestinal symptoms) and one a severe adverse event (thrombocytopenia, bruising), which resolved after discontinuing PSGAG. PSGAG is most commonly administered along with other medications and rehabilitation therapies. The present study demonstrates that SC administration of PSGAG is well tolerated in most of the dogs, with primarily mild, self-resolving adverse events.

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