Paola Castrogiovanni

New perspectives for articular cartilage repair treatment through tissue engineering: A contemporary review

In this paper review we describe benefits and disadvantages of the established methods of cartilage regeneration that seem to have a better long-term effectiveness. We illustrated the anatomical aspect of the knee joint cartilage, the current state of cartilage tissue engineering, through mesenchymal stem cells and biomaterials, and in conclusion we provide a short overview on the rehabilitation after articular cartilage repair procedures. Adult articular cartilage has low capacity to repair itself, and thus even minor injuries may lead to progressive damage and osteoarthritic joint degeneration, resulting in significant pain and disability. Numerous efforts have been made to develop tissue-engineered grafts or patches to repair focal chondral and osteochondral defects, and to date several researchers aim to implement clinical application of cell-based therapies for cartilage repair. A literature review was conducted on PubMed, Scopus and Google Scholar using appropriate keywords, examining the current literature on the well-known tissue engineering methods for the treatment of knee osteoarthritis.

Osteoarthritis in the XXIst Century: Risk Factors and Behaviours that Influence Disease Onset and Progression

Osteoarthritis (OA) is a growing public health problem across the globe, affecting more than half of the over 65 population. In the past, OA was considered a wear and tear disease, leading to the loss of articular cartilage and joint disability. Nowadays, thanks to advancements in molecular biology, OA is believed to be a very complex multifactorial disease. OA is a degenerative disease characterized by “low-grade inflammation” in cartilage and synovium, resulting in the loss of joint structure and progressive deterioration of cartilage. Although the disease can be dependent on genetic and epigenetic factors, sex, ethnicity, and age (cellular senescence, apoptosis and lubricin), it is also associated with obesity and overweight, dietary factors, sedentary lifestyle and sport injuries. The aim of this review is to highlight how certain behaviors, habits and lifestyles may be involved in the onset and progression of OA and to summarize the principal risk factors involved in the development of this complicated joint disorder.

Treatment with rapamycin ameliorates clinical and histological signs of protracted relapsing experimental allergic encephalomyelitis in Dark Agouti rats and induces expansion of peripheral CD4+CD25+Foxp3+ regulatory T cells

We have presently evaluated the effects of the immunomodulatory drug rapamycin on the course of protracted relapsing experimental allergic encephalomyelitis (PR-EAE) in Dark Agouti (DA) rats, which serves as a preclinical model of multiple sclerosis. The data show that the oral administration of rapamycin at 3 mg/kg for 28 consecutive days significantly ameliorated the course of PR-EAE in DA rats. The rats that received the medication had significantly lower clinical cumulative scores and shorter duration of the disease than did the control rats treated with the vehicle. The milder course of the disease was associated with a reduction of the histopathological signs associated to EAE: increased percentage of splenic CD4+CD25 + Foxp3+ Tregs and concomitant reduction of splenic CD8+T cells. These data suggest that rapamycin has pharmacological potential worthy of consideration in the treatment of MS patients.

Effects of dietary extra-virgin olive oil on oxidative stress resulting from exhaustive exercise in rat skeletal muscle: a morphological study.

Physical exercise induces oxidative stress through production of reactive oxygen species and can cause damage to muscle tissue. Oxidative stress, resulting from exhaustive exercise is high and improvement of antioxidant defenses of the body may ameliorate damage caused by free radicals. Extra-virgin olive oil is widely considered to possess anti-oxidative properties. The aim of this study was to determine if extra-virgin olive oil improved the adaptive responses in conditions of oxidative stress. Twenty-four 12-week-old male Sprague-Dawley rats were divided in three groups: (1) rats fed with standard chow and not subjected to physical exercise; (2) rats fed with standard chow and subjected to exhaustive exercise; (3) rats fed with a diet rich in oleic acid, the major component of extra-virgin olive oil, and subjected to exhaustive exercise. Exhaustive exercise consisted of forced running in a five-lane 10° inclined treadmill at a speed of 30 m/min for 70-75 min. We studied some biomarkers of oxidative stress and of antioxidant defenses, histology and ultrastructure of the Quadriceps femoris muscle (Rectus femoris). We observed that, in rats of group 3, parameters indicating oxidative stress such as hydroperoxides and thiobarbituric acid-reactive substances decreased, parameters indicating antioxidant defenses of the body such as non-enzymatic antioxidant capacity and Hsp70 expression increased, and R. femoris muscle did not show histological and ultrastructural alterations. Results of this study support the view that extra-virgin olive oil can improve the adaptive response of the body in conditions of oxidative stress.

Physical activity ameliorates cartilage degeneration in a rat model of aging: A study on lubricin expression

Osteoarthritis (OA) is a common musculoskeletal disorder characterized by slow progression and joint tissue degeneration. Aging is one of the most prominent risk factors for the development and progression of OA. OA is not, however, an inevitable consequence of aging and age‐related changes in the joint can be distinguished from those that are the result of joint injury or inflammatory disease. The question that remains is whether OA can be prevented by undertaking regular physical activity. Would moderate physical activity in the elderly cartilage (and lubricin expression) comparable to a sedentary healthy adult? In this study we used physical exercise in healthy young, adult, and aged rats to evaluate the expression of lubricin as a novel biomarker of chondrocyte senescence. Immunohistochemistry and western blotting were used to evaluate the expression of lubricin in articular cartilage, while enzyme‐linked immunosorbent assay was used to quantify lubricin in synovial fluid. Morphological evaluation was done by histology to monitor possible tissue alterations. Our data suggest that moderate physical activity and normal mechanical joint loading in elderly rats improve tribology and lubricative properties of articular cartilage, promoting lubricin synthesis and its elevation in synovial fluid, thus preventing cartilage degradation compared with unexercised adult rats.

Biomarkers of Chondrocyte Apoptosis and Autophagy in Osteoarthritis

Cell death with morphological and molecular features of apoptosis has been detected in osteoarthritic (OA) cartilage, which suggests a key role for chondrocyte death/survival in the pathogenesis of OA. Identification of biomarkers of chondrocyte apoptosis may facilitate the development of novel therapies that may eliminate the cause or, at least, slow down the degenerative processes in OA. The aim of this review was to explore the molecular markers and signals that induce chondrocyte apoptosis in OA. A literature search was conducted in PubMed, Scopus, Web of Science and Google Scholar using the keywords chondrocyte death, apoptosis, osteoarthritis, autophagy and biomarker. Several molecules considered to be markers of chondrocyte apoptosis will be discussed in this brief review. Molecular markers and signalling pathways associated with chondroycte apoptosis may turn out to be therapeutic targets in OA and approaches aimed at neutralizing apoptosis-inducing molecules may at least delay the progression of cartilage degeneration in OA.

Pregnancy, embryo-fetal development and nutrition: physiology around fetal programming

Abstract The purpose of this brief narrative review is to highlight the role of nutrition during the gestation period. We focused on the possible effects of imbalance of some nutrients in normal course of pregnancy and embryonic

Post-Traumatic Caspase-3 Expression in the Adjacent Areas of Growth Plate Injury Site: A Morphological Study

The epiphyseal plate is a hyaline cartilage plate that sits between the diaphysis and the epiphysis. The objective of this study was to determine the impact of an injury in the growth plate chondrocytes through the study of histological morphology, immunohistochemistry, histomorphometry and Western Blot analyses of the caspase-3 and cleaved PARP-1, and levels of the inflammatory cytokines, Interleukin-6 (IL-6) and Tumor Necrosis Factor alpha (TNF-α), in order to acquire more information about post-injury reactions of physeal cell turnover. In our results, morphological analysis showed that in experimental bones, neo-formed bone trabeculae—resulting from bone formation repair—invaded the growth plate and reached the metaphyseal bone tissue (bone bridge), and this could result in some growth arrest. We demonstrated, by ELISA, increased expression levels of the inflammatory cytokines IL-6 and TNF-α. Immunohistochemistry, histomorphometry and Western Blot analyses of the caspase-3 and cleaved PARP-1 showed that the physeal apoptosis rate of the experimental bones was significantly higher than that of the control ones. In conclusion, we could assume that the inflammation process causes stress to chondrocytes that will die as a biological defense mechanism, and will also increase the survival of new chondrocytes for maintaining cell homeostasis. Nevertheless, the exact stimulus leading to the increased apoptosis rate, observed after injury, needs additional research to understand the possible contribution of chondrocyte apoptosis to growth disturbance.

Somitogenesis: From somite to skeletal muscle

Myogenesis is controlled by an elaborate system of extrinsic and intrinsic regulatory mechanisms in all development stages. The aim of this review is to provide an overview of the different stages of myogenesis and muscle differentiation in mammals, starting from somitogenesis and analysis of the different portions that constitute the mature somite. Particular attention was paid to regulatory genes, in addition to mesodermal stem cells, which represent the earliest elements of myogenesis. Finally, the crucial role of growth factors, molecules of vital importance in contractile regulation, hormones and their function in skeletal muscle differentiation, growth and metabolism, and the role played by central nervous system, are discussed.

Histochemistry as a unique approach for investigating normal and osteoarthritic cartilage

In this review article, we describe benefits and disadvantages of the established histochemical methods for studying articular cartilage tissue under normal, pathological and experimental conditions. We illustrate the current knowledge on cartilage tissue based on histological and immunohistochemical aspects, and in conclusion we provide a short overview on the degeneration of cartilage, such as osteoarthritis. Adult articular cartilage has low capacity to repair itself, and thus even minor injuries may lead to progressive damage and osteoarthritic joint degeneration, resulting in significant pain and disability. Numerous efforts have been made to implement the knowledge in the study of cartilage in the last years, and histochemistry proved to be an especially powerful tool to this aim.