Levels of Matrix-Degrading Enzymes and Lubricin in Patients With Degenerative Joint Disease Requiring Arthroplasty

Total joint arthroplasty (TJA) of the hip or knee (THA and TKA) is the primary surgical intervention for individuals with degenerative joint disease (DJD). Although it is commonly thought that shear force on the joint causes the degradation of articular cartilage, it is possible that there are other factors that contribute to the progression of DJD. It is plausible that specific enzymes that degrade the joint are upregulated, or conversely, there is downregulation of enzymes critical for joint lubrication. The aim of this study is to profile collagenase-1, elastase, heparanase, and lubricin levels in patients undergoing TJA in order to determine potential preexisting dysregulation that contributes to the pathogenesis of DJD. Deidentified blood samples were obtained from patients undergoing TJA 1 day pre- and 1 day postoperatively. Plasma samples were analyzed using enzyme-linked immunosorbent assay kits for elastase, collagenase-1, heparanase, and lubricin. In comparison to healthy controls, there were significant increases in circulating collagenase-1, elastase, and lubricin levels in both the preoperative and postoperative samples. There were no significant differences in heparanase levels in the preoperative or postoperative samples. Comparing the preoperative versus postoperative patient samples, only lubricin demonstrated a significant change. The results of this study confirm that patients undergoing TJA have preexisting alterations in the levels of matrix-degrading enzymes and lubricin. The alterations observed in this study may provide insight into the pathogenesis of DJD.

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Periprosthetic fractures of the knee: a comprehensive review

European Journal of Orthopaedic Surgery & Traumatology ◽

10.1007/s00590-019-02582-5 ◽

2019 ◽

Vol 30 (3) ◽

pp. 387-399 ◽

Cited By ~ 3

Author(s):

Vadim Benkovich ◽

Yuri Klassov ◽

Boris Mazilis ◽

Shlomo Bloom

Keyword(s):

Knee Arthroplasty ◽

Rare Complication ◽

Treatment Options ◽

Degenerative Joint Disease ◽

Joint Arthroplasty ◽

Joint Disease ◽

Periprosthetic Fractures ◽

Complex Injury ◽

Life Threatening ◽

Total Knee

AbstractDemographic changes have resulted in an increase in the number of older patients diagnosed with degenerative joint disease. Developments in the field of joint arthroplasty allow a broader population to improve their lifestyles. An increased demand for knee arthroplasty has led to a rise in operations performed worldwide. Although there has been a constant propagation of technology and an increase in medical staffing at a professional level, many patients still encounter complications. Though rare, these factors may lead to life-threatening scenarios and a devastating effect on the success of the operation. One such rare complication includes periprosthetic fractures around the knee, a complex injury which requires a cautious and experienced approach. In this review, we analyze the prevalence, risk factors and classification, investigation and treatment options for periprosthetic fractures with total knee arthroplasty.

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Blocking of checkpoint receptor PD-L1 aggravates osteoarthritis in macrophage-dependent manner in the mice model

International Journal of Immunopathology and Pharmacology ◽

10.1177/2058738418820760 ◽

2019 ◽

Vol 33 ◽

pp. 205873841882076 ◽

Cited By ~ 3

Author(s):

Shenghou Liu ◽

Jiqiang Mi ◽

Wenguang Liu ◽

Shipeng Xiao ◽

Chunzheng Gao

Keyword(s):

Inflammatory Cytokine ◽

Cruciate Ligament ◽

Mrna Level ◽

Degenerative Joint Disease ◽

Joint Disease ◽

Enzyme Linked Immunosorbent Assay ◽

Dependent Manner ◽

Mice Model ◽

Safranin O ◽

Factor Α

As a chronic degenerative joint disease, osteoarthritis is among the most common diseases all over the world. In osteoarthritis, inflammation plays an important role in the generation of joint symptoms and the development of disease. When the programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint is blocked, the antitumor immunity will be enhanced. We aim to illustrate the function of PD-L1 in osteoarthritis. Osteoarthritis in mice was induced by the injection of collagenase or anterior cruciate ligament transection (ACLT). Anti-PD-L1 was employed to block the signal of PD-L1. Knee joints histological sections were stained by Safranin-O. The level of cytokine was checked by enzyme-linked immunosorbent assay (ELISA) and mRNA level was shown by quantitative reverse transcriptase polymerase chain reaction. The blockade of PD-L1 signal up-regulated inflammatory response and promoted the development of osteoarthritis in mice. The inflammatory cytokine interleukin-6 and tumor necrosis factor-α expression were promoted by PD-L1 blocking in macrophages. Osteoarthritis was aggravated when the expression of inflammatory cytokine is elevated in macrophages. Our results indicated that the blockade of PD-L1 signal in macrophages elevates the expression of inflammatory cytokine and promotes the development of osteoarthritis in mice, which could be utilized as a potential diagnostic and therapeutic target for osteoarthritis patients.

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Sports Activity Following Cementless Metaphyseal Hip Joint Arthroplasty

Journal of Human Kinetics ◽

10.1515/hukin-2017-0112 ◽

2017 ◽

Vol 60 (1) ◽

pp. 225-232

Author(s):

Szymon Czech ◽

Jacek Hermanson ◽

Piotr Rodak ◽

Tomasz Stołtny ◽

Łukasz Rodak ◽

...

Keyword(s):

Physical Activity ◽

Hip Joint ◽

Degenerative Joint Disease ◽

Joint Arthroplasty ◽

Joint Disease ◽

Harris Hip Score ◽

Joint Diseases ◽

Sports Activity ◽

Level Of Functioning ◽

Degenerative Joint Diseases

Abstract An adequate level of physical activity has a substantial effect on both mental and physical human health. Physical activity is largely dependent on the function of the musculoskeletal and articular system. One of the most frequent diseases of this system is degenerative joint disease. Due to the changing and more demanding lifestyles and patients’ willingness to be involved in sports activity, the expectations of hip joint arthroplasty are becoming increasingly high. Alleviating pain ceases to be the only reason for which patients choose surgical interventions, while the expectations often include involvement in various sports. Only few studies contain recommendations concerning the frequency, type and intensity of sports activity which are acceptable after hip joint arthroplasty. The aim of the study was to evaluate function and physical activity of people following cementless short-stem hip joint arthroplasty in the observation of at least five years. The study group comprised 106 patients who underwent total hip arthroplasty due to degenerative joint diseases, chosen according to inclusion criteria. Patients underwent routine physical examinations following the Harris Hip Score protocol, responded to the UCLA scale and questionnaires concerning pre-surgical and current physical activity. Our results demonstrated that hip joint arthroplasty in people suffering from degenerative joint diseases has a beneficial effect on their level of functioning and physical activity. Although physical activity and the level of functioning obviously reduced as a person aged, the level of physical activity continued to be very high in both groups, with function of the hip joint evaluated as very good.

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Anticoagulant Therapy for the Treatment of Idiopathic Osteonecrosis.

Blood ◽

10.1182/blood.v106.11.919.919 ◽

2005 ◽

Vol 106 (11) ◽

pp. 919-919

Author(s):

Saaib Al Shehadat ◽

Gregory R. Bociek ◽

William Haire

Keyword(s):

Pain Relief ◽

Anticoagulant Therapy ◽

Surgical Intervention ◽

Motor Vehicle ◽

Venous Pressure ◽

Anticoagulation Therapy ◽

Degenerative Joint Disease ◽

Joint Disease ◽

Severe Toxicity ◽

Orthopedic Surgeon

Abstract Background: Studies suggest that thrombosis may play an important etiologic role in adults with idiopathic osteonecrosis. Thrombotic occlusion in the bone leads to increased intraosseus venous pressure, reduced arterial flow, and ultimately hypoxic bone death. Total joint arthroplasty is the standard treatment for advanced osteonecrosis. The majority of untreated patients with idiopathic osteonecrosis will progress to significant degenerative disease. We report our experience in five consecutive patients who were referred to our institute and were treated with anticoagulant therapy instead of surgical intervention. Methods: Five adult patients (median age 38 years old, range 28–49 years) were evaluated first by an orthopedic surgeon for knee or hip pain. The diagnosis of osteonecrosis was confirmed by Magnetic Resonance Image (MRI) interpreted in all cases by both a radiologist and an orthopedic surgeon. Osteonecrosis was designated as idiopathic after eliminating other known associated factors, mainly drugs (glucocorticoids) or diseases (alcoholism, sickle cell disease). The response to treatment was measured by pain relief, bone imaging stability or improvement, and subsequent need for surgical intervention. Treatment was discontinued if the patient developed severe toxicity or disease progression requiring surgical intervention. Four patients were treated with warfarin with a target international normalized ratio (INR) of 2–3, while one patient was treated with enoxaparin (1 mg/kg twice a day). Patients were followed up every three months by both a hematologist and an orthopedic surgeon, and MRI evaluation was performed at three month intervals for one year or when symptoms worsened. After achieving pain relief and stability of lesions on MRI, patients were given the choice of discontinuing the treatment. Results: Three out of four patients on warfarin and the patient on enoxaparin had pain improvement within three months of initiating therapy. All patients reported a reduction of pain at a median of 7.5 months (6–9 months). MRI revealed disease stability in those patients within three months, and some radiographic signs of improvement at 9 months. Complete resolution of imaging abnormalities was seen in 5 years in one patient. Patients tolerated the therapy well without any major toxicity and decided to continue the anticoagulation therapy. One patient preferred to discontinue therapy after 4.5 years, and continued to be asymptomatic 10 months later. The fifth patient had bilateral distal femoral and proximal tibial osteonecrosis. The patient had severe degenerative joint disease involving the right knee from previous motor vehicle accident. The patient eventually underwent right knee arthroplasty for severe pain, and the microscopic examination of the bone and debridement tissue from the joint replacement procedure showed focal avascular necrosis and features of degenerative joint disease. The patient resumed the warfarin therapy postoperatively with stability of imaging abnormalities on the left side after 3.5 years of continuous therapy. Warfarin was replaced by aspirin with eighteen months of follow up, the patient continued to be asymptomatic with stable imaging abnormalities of the left leg. Conclusion: The findings suggest that anticoagulation therapy may benefit patients with early stage of idiopathic osteonecrosis, and may delay or eliminate the need for surgical intervention. Further studies are warranted in he future to compare different anticoagulants with placebo.

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Dysregulation of Tissue Factor, Thrombin-Activatable Fibrinolysis Inhibitor, and Fibrinogen in Patients Undergoing Total Joint Arthroplasty

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029617700998 ◽

2017 ◽

Vol 23 (8) ◽

pp. 967-972 ◽

Cited By ~ 5

Author(s):

Christopher Wanderling ◽

Jeffrey Liles ◽

Elissa Finkler ◽

Peter Carlsgaard ◽

William Hopkinson ◽

...

Keyword(s):

Tissue Factor ◽

Total Joint Arthroplasty ◽

Surgical Intervention ◽

Perioperative Complications ◽

Joint Arthroplasty ◽

Enzyme Linked Immunosorbent Assay ◽

Activity Assay ◽

Thrombin Activatable Fibrinolysis Inhibitor ◽

Common Procedure ◽

Fibrinolysis Inhibitor

Total joint arthroplasty (TJA) of the hip or knee (THA, TKA) has become an increasingly common procedure. While TJA is a successful treatment for individuals experiencing degenerative joint diseases, it is well known that one of the most common perioperative complications of TJA is deep venous thrombosis (DVT). To profile tissue factor (TF), microparticle-tissue factor (MP-TF), thrombin-activatable fibrinolysis inhibitor (TAFI), and fibrinogen levels in patients undergoing TJA to determine potential preexisting Hemostatic dysregulation. De-identified blood samples were obtained from patients undergoing TJA 1 day pre- and 1 day postprocedure. Plasma samples were analyzed using enzyme-linked immunosorbent assay kits for fibrinogen, TAFI, TF, and MP-TF; fibrinogen levels were also assessed using a clot-based activity assay. In comparison with healthy controls, there were significant increases of fibrinogen and MP-TF levels, while there were significant decreases in TF and TAFI levels in the preoperative and postoperative patients. Comparing the pre versus postoperative patients, no significant differences were found; interestingly, however, surgical intervention exacerbated the changes found in the preoperative samples compared to the controls. The results of this study confirm that patients undergoing TJA have preexisting alterations in the fibrinolytic system. Surgical intervention tended to exacerbate these changes. The alterations observed in this study may provide insight as to why TJA is associated with higher rates of DVT and thromboembolism.

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CircRNA-MSR Regulates LPS-Induced C28/I2 Chondrocyte Injury through miR-643/MAP2K6 Signaling Pathway

Cartilage ◽

10.1177/19476035211044826 ◽

2021 ◽

pp. 194760352110448

Author(s):

Zhen Jia ◽

Qing-Jun Wei

Keyword(s):

Cell Proliferation ◽

Degenerative Joint Disease ◽

Mitogen Activated Protein Kinase ◽

Joint Disease ◽

Luciferase Reporter ◽

Circular Rnas ◽

Enzyme Linked Immunosorbent Assay ◽

Luciferase Reporter Gene ◽

Rna Fish

Objective Osteoarthritis (OA) is a degenerative joint disease characterized by deterioration of articular cartilage functions. Previous studies have confirmed the role of circular RNAs (circRNAs) in OA, but the role of mechanical stress–related circRNA (circRNA-MSR) in OA is unknown. Design The human chondrocytes C28/I2 were cultured and treated with lipopolysaccharide (LPS) to establish the OA model. The mRNA and protein levels were measured by qRT-PCR or Western blot. Cell viability was analyzed by MTT assay. Flow cytometry was carried out to detect cell apoptosis. The levels of TNF-α, IL-1β, and IL-6 were determined by enzyme-linked immunosorbent assay (ELISA). Pull-down assay was conducted to measure circRNA-MSR-related miRNA. Dual-luciferase reporter gene detection was performed to detect the target relationships between miR-643 and circRNA-MSR or Mitogen-activated protein kinase kinase 6 (MAP2K6). The RNA–fluorescence in situ hybridization (RNA-FISH) assay was conducted to verify the localization of circRNA-MSR and miR-643. Results The expressions of circRNA-MSR were upregulated in LPS stimulated C28/I2 cells. Knockdown of circRNA-MSR can inhibit LPS-induced apoptosis, inflammatory response, and extracellular matrix (ECM) degradation, and promote cell C28/I2 cells proliferation. Moreover, circRNA-MSR directly targeted miR-643. RNA-FISH exhibited that circRNA-MSR may act as a competing endogenous RNA (ceRNA) of miR-643. Over-expression of miR-643 could alleviate LPS-induced C28/I2 chondrocyte injury and promote cell proliferation. Besides, miR-643 directly bound to MAP2K6 mRNA. MiR-643 inhibition or MAP2K6 overexpression can reverse the role of circRNA-MSR knockdown on LPS-treated chondrocytes. Conclusion circRNA-MSR can upregulate MAP2K6 by targeting miR-643, thereby inhibiting cell proliferation and promoting apoptosis of C28/I2 cells.

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Interrelationship of Osteopontin, MMP-9 and ADAMTS4 in Patients With Osteoarthritis Undergoing Total Joint Arthroplasty

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029620964864 ◽

2020 ◽

Vol 26 ◽

pp. 107602962096486

Author(s):

Hannah Slovacek ◽

Rajan Khanna ◽

Pavel Poredos ◽

Mateja Jezovnik ◽

Debra Hoppensteadt ◽

...

Keyword(s):

Total Joint Arthroplasty ◽

Joint Damage ◽

Cartilage Degradation ◽

Degenerative Joint Disease ◽

Joint Arthroplasty ◽

Joint Disease ◽

Promising Area ◽

Thrombotic Complications ◽

A Disintegrin And Metalloproteinase ◽

The Relationship

Osteoarthritis (OA) is a degenerative joint disease characterized by loss of articular cartilage, inflammation and pain, which sometimes necessitates total joint arthroplasty (TJA). Profiling biomarkers of cartilage degradation and inflammation is a promising area of research to understand the pathogenesis of OA. This study aims to report the post-operative fluctuations of 3 biomarkers of OA, osteopontin (OPN), matrix metalloproteinase-9 (MMP-9), and ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs 4), in patients undergoing TJA to further define the interaction among these biomarkers and delineate their role in OA pathogenesis. OPN is an extracellular matrix (ECM) glycoprotein with increased activity in OA and joint damage and is upregulated by either inflammation or cleavage by MMPs and thrombin. MMP-9 is known to cleave OPN and is upregulated by inflammatory markers, such as IL-1, IL-6 and CRP. ADAMTS4 is an enzyme that degrades aggrecan, a major component of cartilage. These biomarkers were measured in deidentified blood samples collected on the day of surgery, 1 day post-operatively, and day 5-7 post-operatively. MMP-9 and OPN levels were significantly elevated at all times, and ADAMTS4 was significantly decreased at baseline versus controls. OPN and ADAMTS4 inversely fluctuated post-operatively, indicating an interrelation between these 2 biomarkers. This study suggests that the upregulation of MMP-9 and therefore OPN then results in the downregulation of ADAMTS4. The relationship between OPN and thrombin also highlights the importance of monitoring for thrombotic complications. These biomarkers, along with thrombin-mediated cleavage products, may be helpful in the prognostic management of OA patients.

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ROLE OF PANCHATIKTA KSHEERGHRITA BASTI IN THE MANAGEMENT OF SANDHIGATA VATA WITH SPECIAL TO OSTEOARTHRITIS: A CASE STUDY

National Journal of Research in Ayurved Science ◽

10.52482/ayurlog.v6i06.225 ◽

2018 ◽

Vol 6 (06) ◽

Author(s):

Kalpana Pandurang Rathod

Keyword(s):

Surgical Intervention ◽

Modern Medicine ◽

Degenerative Joint Disease ◽

Joint Disease ◽

Geriatric Population ◽

Joint Replacement Surgery ◽

Replacement Surgery ◽

Total Knee

Ageing is a process of physical, psychological and social change in multi dimensional aspect. Geriatric health care is very important .Sandhigata Vata i.e. osteoarthritis is also known as degenerative joint disease. Majority of geriatric population suffer from Sandhigata Vata. Modern medicine has limitation in treating Osteoarthritis and has many adverse effects with its prolonged use. Now in the era of TKR (Total Knee Joint Replacement) Surgery, but due to some underlying systemic illness, financial constrains it is not possible to opt for surgical intervention.. In Ayurveda it is mentioned that in Vardhakya Avastha all Dhatus undergo Kshay leading to Dhatukshayaj Vatprakopa Samprapti. In Sandhigata Vata there is Kshay of Asthidhatu. Bastichikitsa is considered to be Shreshtha(best) in Vata dosha Chikitsa. In the present case Panchatikta Ksheerbasti along with sarpi (Ghee)was given in the patient suffering from OA for 30days. Panchatikta Ksheerbasti showed symptomatically good result in Sandhigat Vata.

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Management of Early Osteoarthritis

10.5772/intechopen.93582 ◽

2020 ◽

Author(s):

Ahmed Mostafa Kotb Aziz

Keyword(s):

Cost Effective ◽

Cyst Formation ◽

Degenerative Joint Disease ◽

Joint Arthroplasty ◽

Joint Disease ◽

Treatment Modalities ◽

Cost Effective Treatment ◽

Inflammatory Drugs ◽

Lifestyle Physical Activity

Osteoarthritis (OA) is a chronic degenerative joint disease of dynamic pathology with multiple etiologies. It involves progressive process of softening, loss of articular cartilage, subchondral bone sclerosis, development of osteophytes, and cyst formation. OA usually contributes to decreased activity associated with aging, secondary to diminished function and pain, thus consequently impairing quality of life. It is well established that pain due to OA, swelling, or stiffness can make it difficult for individuals to perform simple daily living activities. Although OA is not curable, a variety of treatment modalities are available to improve symptoms. Main elements include pain management maneuvers, education, changing lifestyle physical activity (PA), and weight reduction in case of overweight. Although total joint arthroplasty (TJA) is considered a cost-effective treatment for people with OA, TJA should only be considered after failure of conservative treatments. Symptoms of OA are usually managed by either pharmachological or nonpharmachological protocols; joint replacement surgeries are considered in advanced cases. Analgesics remain the keystone of pharmacological treatment for OA symptoms, including paracetamol, topical and oral nonsteroidal anti-inflammatory drugs (NSAIDs), and opioids. However, benefits from paracetamol and opioids are minimal, and NSAIDs are not ideal for many patients because they have many side-effects. Intra-articular therapies such as corticosteroids are also commonly used, though usually with short-term benefits.

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Transcription Factors in Cartilage Homeostasis and Osteoarthritis

Biology ◽

10.3390/biology9090290 ◽

2020 ◽

Vol 9 (9) ◽

pp. 290

Author(s):

Margot Neefjes ◽

Arjan P. M. van Caam ◽

Peter M. van der Kraan

Keyword(s):

Gene Expression ◽

Extracellular Matrix ◽

Transcription Factors ◽

Degenerative Joint Disease ◽

Joint Disease ◽

Cell Type ◽

Extracellular Signals ◽

Cartilage Homeostasis ◽

Matrix Metabolism ◽

Insight Into

Osteoarthritis (OA) is the most common degenerative joint disease, and it is characterized by articular cartilage loss. In part, OA is caused by aberrant anabolic and catabolic activities of the chondrocyte, the only cell type present in cartilage. These chondrocyte activities depend on the intra- and extracellular signals that the cell receives and integrates into gene expression. The key proteins for this integration are transcription factors. A large number of transcription factors exist, and a better understanding of the transcription factors activated by the various signaling pathways active during OA can help us to better understand the complex etiology of OA. In addition, establishing such a profile can help to stratify patients in different subtypes, which can be a very useful approach towards personalized therapy. In this review, we discuss crucial transcription factors for extracellular matrix metabolism, chondrocyte hypertrophy, chondrocyte senescence, and autophagy in chondrocytes. In addition, we discuss how insight into these factors can be used for treatment purposes.

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