The worldwide epidemic of obesity has brought considerable attention to research aimed at understanding the biology of adipocytes (fat cells) and the events occurring in adipose tissue (fat) and in the bodies of obese individuals. Accumulating evidence indicates that obesity causes chronic low-grade inflammation and that this contributes to systemic metabolic dysfunction that is associated with obesity-linked disorders. Adipose tissue functions as a key endocrine organ by releasing multiple bioactive substances, known as adipose-derived secreted factors or adipokines, that have pro-inflammatory or anti-inflammatory activities. Dysregulated production or secretion of these adipokines owing to adipose tissue dysfunction can contribute to the pathogenesis of obesity-linked complications. In this Review, we focus on the role of adipokines in inflammatory responses and discuss their potential as regulators of metabolic function.

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Adipokines in inflammation and metabolic disease

There has been much effort recently to define the role of adipocytokines, which are soluble mediators derived mainly from adipocytes (fat cells), in the interaction between adipose tissue, inflammation and immunity. The adipocytokines adiponectin and leptin have emerged as the most abundant adipocyte products, thereby redefining adipose tissue as a key component not only of the endocrine system, but also of the immune system. Indeed, as we discuss here, several adipocytokines have a central role in the regulation of insulin resistance, as well as many aspects of inflammation and immunity. Other adipocytokines, such as visfatin, have only recently been identified. Understanding this rapidly growing family of mainly adipocyte-derived mediators might be of importance in the development of new therapies for obesity-associated diseases.

Adipocytokines: mediators linking adipose tissue, inflammation and immunity.

https://lup.lub.lu.se/search/ws/files/2193815/4587178.pdf

OARSI guidelines for the non-surgical management of knee osteoarthritis

The architecture of an engineered tissue substitute plays an important role in modulating tissue growth. A novel poly(D,L-lactide-co-glycolide) (PLGA) structure with a unique architecture produced by an electrospinning process has been developed for tissue-engineering applications. Electrospinning is a process whereby ultra-fine fibers are formed in a high-voltage electrostatic field. The electrospun structure, composed of PLGA fibers ranging from 500 to 800 nm in diameter, features a morphologic similarity to the extracellular matrix (ECM) of natural tissue, which is characterized by a wide range of pore diameter distribution, high porosity, and effective mechanical properties. Such a structure meets the essential design criteria of an ideal engineered scaffold. The favorable cell-matrix interaction within the cellular construct supports the active biocompatibility of the structure. The electrospun nanofibrous structure is capable of supporting cell attachment and proliferation. Cells seeded on this structure tend to maintain phenotypic shape and guided growth according to nanofiber orientation. This novel biodegradable scaffold has potential applications for tissue engineering based upon its unique architecture, which acts to support and guide cell growth.

Electrospun nanofibrous structure: A novel scaffold for tissue engineering

MUCKE aims to mine a large volume of images, to structure them conceptually and to use this conceptual structuring in order to improve large-scale image retrieval. The last decade witnessed important progress concerning low-level image representations. However, there are a number problems which need to be solved in order to unleash the full potential of image mining in applications. The central problem with low-level representations is the mismatch between them and the human interpretation of image content. This problem can be instantiated, for instance, by the incapability of existing descriptors to capture spatial relationships between the concepts represented or by their incapability to convey an explanation of why two images are similar in a content-based image retrieval framework. We start by assessing existing local descriptors for image classification and by proposing to use co-occurrence matrices to better capture spatial relationships in images. The main focus in MUCKE is on cleaning large scale Web image corpora and on proposing image representations which are closer to the human interpretation of images. Consequently, we introduce methods which tackle these two problems and compare results to state of the art methods. Note: some aspects of this deliverable are withheld at this time as they are pending review. Please contact the authors for a preview.

http://ieeexplore.ieee.org/iel2/4524/12820/00592460.pdf

Image Processing

We demonstrate the direct involvement of increased collagenase activity in the cleavage of type II collagen in osteoarthritic human femoral condylar cartilage by developing and using antibodies reactive to carboxy-terminal (COL2-3/4C(short)) and amino-terminal (COL2-1/4N1) neoepitopes generated by cleavage of native human type II collagen by collagenase matrix metalloproteinase (MMP)-1 (collagenase-1), MMP-8 (collagenase-2), and MMP-13 (collagenase-3). A secondary cleavage followed the initial cleavage produced by these recombinant collagenases. This generated neoepitope COL2-1/4N2. There was significantly more COL2-3/4C(short) neoepitope in osteoarthritis (OA) compared to adult nonarthritic cartilages as determined by immunoassay of cartilage extracts. A synthetic preferential inhibitor of MMP-13 significantly reduced the unstimulated release in culture of neoepitope COL2-3/4C(short) from human osteoarthritic cartilage explants. These data suggest that collagenase(s) produced by chondrocytes is (are) involved in the cleavage and denaturation of type II collagen in articular cartilage, that this is increased in OA, and that MMP-13 may play a significant role in this process.

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Enhanced cleavage of type II collagen by collagenases in osteoarthritic articular cartilage.

The adipokine resistin is suggested to be an important link between obesity and insulin resistance. In the present study, we assessed the impact of resistin as inflammatogenic cytokine in the setting of arthritis. In vitro experiments on human PBMC were performed to assess cytokine response and transcription pathways of resistin-induced inflammation. Proinflammatory properties of resistin were evaluated in animal model by intra-articular injection of resistin followed by histological evaluation of the joint. Levels of resistin were assessed by ELISA in 74 paired blood and synovial fluid samples of patients with rheumatoid arthritis. Results were compared with the control group comprised blood samples from 34 healthy individuals and 21 synovial fluids from patients with noninflammatory joint diseases. We now show that resistin displays potent proinflammatory properties by 1) strongly up-regulating IL-6 and TNF-α, 2) responding to TNF-α challenge, 3) enhancing its own activity by a positive feedback, and finally 4) inducing arthritis when injected into healthy mouse joints. Proinflammatory properties of resistin were abrogated by NF-κB inhibitor indicating the importance of NF-κB signaling pathway for resistin-induced inflammation. Resistin is also shown to specifically accumulate in the inflamed joints of patients with rheumatoid arthritis and its levels correlate with other markers of inflammation. Our results indicate that resistin is a new and important member of the cytokine family with potent regulatory functions. Importantly, the identified properties of resistin make it a novel and interesting therapeutic target in chronic inflammatory diseases such as rheumatoid arthritis.

/pdf/resistin-an-adipokine-with-potent-proinflammatory-properties-2g6ad5kby3.pdf

Resistin, an adipokine with potent proinflammatory properties

https://www.oarsijournal.com/article/S1063-4584(05)80017-2/pdf

Osteoarthritis of the knee after injury to the anterior cruciate ligament or meniscus: the influence of time and age.

Objective
To evaluate the effects of moderate exercise on glycosaminoglycan (GAG) content in knee cartilage in subjects at high risk of knee osteoarthritis (OA).

Methods
Forty-five subjects (16 women, mean age 46 years, mean body mass index 26.6 kg/m2) who underwent partial medial meniscus resection 3–5 years previously were randomized to undergo a regimen of supervised exercise 3 times weekly for 4 months or to a nonintervention control group. Cartilage GAG content, an important aspect of the biomechanical properties of cartilage, was estimated by delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC), with results expressed as the change in the T1 relaxation time in the presence of Gd-DTPA (T1[Gd]).

Results
Thirty of 45 patients were examined by dGEMRIC at baseline and followup. The exercise group (n = 16) showed an improvement in the T1(Gd) compared with the control group (n = 14) (15 msec versus −15 msec; P = 0.036). To study the dose response, change in the T1(Gd) was assessed for correlation with self-reported change in physical activity level, and a strong correlation was found in the exercise group (n = 16, rS = 0.70, 95% confidence interval [95% CI] 0.31–0.89) and in the pooled group of all subjects (n = 30, rS = 0.74, 95% CI 0.52–0.87).

Conclusion
This in vivo cartilage monitoring study in patients at risk of knee OA who begin exercising indicates that adult human articular cartilage has a potential to adapt to loading change. Moderate exercise may be a good treatment not only to improve joint symptoms and function, but also to improve the knee cartilage GAG content in patients at high risk of developing OA.

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Positive effects of moderate exercise on glycosaminoglycan content in knee cartilage: A four-month, randomized, controlled trial in patients at risk of osteoarthritis

BACKGROUND: The occurrence of osteoarthritis (OA), associated meniscal injuries, meniscectomy, and patient-related measures for patients treated nonoperatively after anterior cruciate ligament (ACL) injuries have not been well described in the literature in terms of natural history. HYPOTHESIS: Patients with ACL injury can achieve a low occurrence of tibiofemoral OA and good knee function when treated without ACL reconstruction. STUDY DESIGN: Cohort study (prognosis); Level of evidence, 2. METHODS: One hundred consecutive patients with an acute, complete ACL injury were observed for 15 years. All patients were primarily treated with activity modification and without ACL reconstruction. To achieve improved functional stability, supervised physical therapy was initiated early after injury. The patients were examined using anteroposterior weightbearing radiography. The Knee injury and Osteoarthritis Outcome Score (KOOS) was used to quantify knee-related symptoms and knee function. RESULTS: Seventy-nine patients consented to radiographic examination and 93 completed the KOOS questionnaire. Thirteen patients (16%), all of whom were among the 35 patients whose knees were meniscectomized, developed radiographic tibiofemoral OA. In contrast, none of the remaining nonmeniscectomized and radiographed knees developed OA (n = 44) (P < .0001). Sixty-three patients (68%) had an asymptomatic knee. Twenty-two patients (23%) had undergone ACL reconstruction with a mean time of 4 years after injury. CONCLUSION: The study had a favorable long-term outcome regarding incidence of radiographic knee OA, knee function and symptoms, and need for ACL reconstruction. Although risk factors for posttraumatic OA are multifactorial, the primary risk factor that stood out in this study was if a meniscectomy had been performed. Early activity modification and neuromuscular knee rehabilitation might also have been related to the low prevalence of radiographic knee OA. In patients with ACL injury willing to moderate activity level to avoid reinjury, initial treatment without ACL reconstruction should be considered.

Leif Dahlberg

Papers

Enhanced cleavage of type II collagen by collagenases in osteoarthritic articular cartilage.

Resistin, an adipokine with potent proinflammatory properties

Osteoarthritis of the knee after injury to the anterior cruciate ligament or meniscus: the influence of time and age.

Positive effects of moderate exercise on glycosaminoglycan content in knee cartilage: A four-month, randomized, controlled trial in patients at risk of osteoarthritis

Prevalence of tibiofemoral osteoarthritis 15 years after nonoperative treatment of anterior cruciate ligament injury: a prospective cohort study