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1.
Front Sports Act Living ; 6: 1465562, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39371112

RESUMO

The importance of sports and the approval of the Dual Career regulation at the University of Rome "Tor Vergata" are highly significant topics for the well-being and personal development of students. In line with European and international policies, this initiative recognizes the specific needs of student-athletes by offering them tools and flexibility to excel in both sports and academics. However, monitoring student-athletes by Universities requires thorough investigations and the development of initiatives to promote students' adherence to sports practice. Therefore, our study aims to analyze the results of a survey administered to students enrolled at the University of Rome "Tor Vergata" during the academic years 2020/2021, 2021/2022, 2022/2023, and 2023/2024, investigating the effects of the introduction of the Dual Career regulation on the student population. Our preliminary results showed that the introduction of the Dual Career program was associated with a significant increase in the number of students practising sports over the academic years, with greater participation in the academic years 2022/2023 and 2023/2024. Noteworthy, the number of student-athletes who applied to the Dual Career program markedly increased in the last year, with the highest number of enrollments in the macroareas of Medicine and Surgery, Economy, and Engineering. Overall, the Dual Career regulation offers the possibility to plan the study path in a personalized way, dedicated academic support, and flexibility in deadlines, making the University of Rome "Tor Vergata" a model of integration between education and sportiness.

2.
Biomedicines ; 12(10)2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39457530

RESUMO

Biological drugs, including monoclonal antibodies, represent a revolutionary strategy in all fields of medicine, offering promising results even in the treatment of osteoarthritis (OA). However, their safety and efficacy have not been fully validated, highlighting the need for in-depth studies. Therefore, we provided a comprehensive systematic review of the intra-articular use of monoclonal antibodies for the treatment of OA in animal models, reflecting ongoing efforts to advance therapeutic strategies and improve patient outcomes. A systematic literature search was conducted in December 2023 following the PRISMA guidelines, using the Web of Science, Google Scholar, and PUBMED databases. Out of a total of 456, 10 articles were included in the study analyzing intra-articular antibodies and focusing on various targets, including vascular endothelial growth factor (VEGF), nerve growth factor (NGF), interleukin 4-10 (IL4-10), tumor necrosis factor α (TNF-α), a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5), and matrix metalloproteinase 13 (MMP-13). Most studies administered the antibodies weekly, ranging from 1 to 10 injections. Animal models varied, with mean follow-up periods of 8.9 ± 4.1 weeks. The methods of assessing outcomes, including pain and morpho-functional changes, varied. Some studies reported only morphological and immunohistochemical data, while others included a quantitative analysis of protein expression. In conclusion, monoclonal antibodies represent a promising avenue in the treatment of OA, offering targeted approaches to modulate disease pathways. Further research and clinical trials are needed to validate their safety and efficacy, with the potential to revolutionize the management of OA and reduce reliance on prosthetic interventions.

3.
Biomedicines ; 12(9)2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39335461

RESUMO

The aging of the world population is closely associated with an increased prevalence of musculoskeletal disorders, such as osteoporosis, sarcopenia, and osteoarthritis, due to common genetic, endocrine, and mechanical risk factors. These conditions are characterized by degeneration of bone, muscle, and cartilage tissue, resulting in an increased risk of fractures and reduced mobility. Importantly, a crucial role in the pathophysiology of these diseases has been proposed for cellular senescence, a state of irreversible cell cycle arrest induced by factors such as DNA damage, telomere shortening, and mitochondrial dysfunction. In addition, senescent cells secrete pro-inflammatory molecules, called senescence-associated secretory phenotype (SASP), which can alter tissue homeostasis and promote disease progression. Undoubtedly, targeting senescent cells and their secretory profiles could promote the development of integrated strategies, including regular exercise and a balanced diet or the use of senolytics and senomorphs, to improve the quality of life of the aging population. Therefore, our review aimed to highlight the role of cellular senescence in age-related musculoskeletal diseases, summarizing the main underlying mechanisms and potential anti-senescence strategies for the treatment of osteoporosis, sarcopenia, and osteoarthritis.

4.
Int J Mol Sci ; 25(13)2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-39000060

RESUMO

Neurodegenerative diseases (NDs) represent an unsolved problem to date with an ever-increasing population incidence. Particularly, Alzheimer's disease (AD) is the most widespread ND characterized by an accumulation of amyloid aggregates of beta-amyloid (Aß) and Tau proteins that lead to neuronal death and subsequent cognitive decline. Although neuroimaging techniques are needed to diagnose AD, the investigation of biomarkers within body fluids could provide important information on neurodegeneration. Indeed, as there is no definitive solution for AD, the monitoring of these biomarkers is of strategic importance as they are useful for both diagnosing AD and assessing the progression of the neurodegenerative state. In this context, exercise is known to be an effective non-pharmacological management strategy for AD that can counteract cognitive decline and neurodegeneration. However, investigation of the concentration of fluid biomarkers in AD patients undergoing exercise protocols has led to unclear and often conflicting results, suggesting the need to clarify the role of exercise in modulating fluid biomarkers in AD. Therefore, this critical literature review aims to gather evidence on the main fluid biomarkers of AD and the modulatory effects of exercise to clarify the efficacy and usefulness of this non-pharmacological strategy in counteracting neurodegeneration in AD.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Biomarcadores , Exercício Físico , Proteínas tau , Doença de Alzheimer/metabolismo , Doença de Alzheimer/terapia , Humanos , Biomarcadores/metabolismo , Exercício Físico/fisiologia , Peptídeos beta-Amiloides/metabolismo , Proteínas tau/metabolismo , Terapia por Exercício/métodos
5.
PLoS One ; 19(3): e0300888, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38512830

RESUMO

Neuronal death could be responsible for the cognitive impairments found in astronauts exposed to spaceflight, highlighting the need to identify potential countermeasures to ensure neuronal health in microgravity conditions. Therefore, differentiated HT22 cells were exposed to simulated microgravity by random positioning machine (RPM) for 48 h, treating them with a single administration of Trolox, recombinant irisin (r-Irisin) or both. Particularly, we investigated cell viability by MTS assay, Trypan Blue staining and western blotting analysis for Akt and B-cell lymphoma 2 (Bcl-2), the intracellular increase of reactive oxygen species (ROS) by fluorescent probe and NADPH oxidase 4 (NOX4) expression, as well as the expression of brain-derived neurotrophic factor (BDNF), a major neurotrophin responsible for neurogenesis and synaptic plasticity. Although both Trolox and r-Irisin manifested a protective effect on neuronal health, the combined treatment produced the best results, with significant improvement in all parameters examined. In conclusion, further studies are needed to evaluate the potential of such combination treatment in counteracting weightlessness-induced neuronal death, as well as to identify other potential strategies to safeguard the health of astronauts exposed to spaceflight.


Assuntos
Cromanos , Fibronectinas , Ausência de Peso , Fibronectinas/farmacologia , Fibronectinas/metabolismo , Neurônios/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Diferenciação Celular
6.
Geriatrics (Basel) ; 8(5)2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37736892

RESUMO

Good musculoskeletal quality dramatically influences the outcome of an arthroplasty operation in geriatric patients, as well as is a key element for optimal osseointegration. In this context, metallosis is a complication associated with the type of prosthesis used, as implants with a chromium-cobalt interface are known to alter the bone microarchitecture and reduce the ratio of muscle to fat, resulting in lipid accumulation. Therefore, the aim of our study was to investigate possible muscle changes by histological, morphometric, and immunohistochemical analyses in a patient undergoing hip replacement revision with elevated blood and urinary concentrations of chromium and cobalt. Interestingly, the muscle tissue showed significant structural changes and a massive infiltration of adipose tissue between muscle fibers in association with an altered expression pattern of important biomarkers of musculoskeletal health and oxidative stress, such as myostatin and NADPH Oxidase 4. Overall, our results confirm the very serious impact of metallosis on musculoskeletal health, suggesting the need for further studies to adopt a diagnostic approach to identify the cause of metallosis early and eliminate it as part of the prosthesis revision surgery.

7.
Life (Basel) ; 13(7)2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37511798

RESUMO

Space colonization represents the most insidious challenge for mankind, as numerous obstacles affect the success of space missions. Specifically, the absence of gravitational forces leads to systemic physiological alterations, with particular emphasis on the musculoskeletal system. Indeed, astronauts exposed to spaceflight are known to report a significant impairment of bone microarchitecture and muscle mass, conditions clinically defined as osteoporosis and sarcopenia. In this context, space medicine assumes a crucial position, as the development of strategies to prevent and/or counteract weightlessness-induced alterations appears to be necessary. Furthermore, the opportunity to study the biological effects induced by weightlessness could provide valuable information regarding adaptations to spaceflight and suggest potential treatments that can preserve musculoskeletal health under microgravity conditions. Noteworthy, improving knowledge about the latest scientific findings in this field of research is crucial, as is thoroughly investigating the mechanisms underlying biological adaptations to microgravity and searching for innovative solutions to counter spaceflight-induced damage. Therefore, this narrative study review, performed using the MEDLINE and Google Scholar databases, aims to summarize the most recent evidence regarding the effects of real and simulated microgravity on the musculoskeletal system and to discuss the effectiveness of the main defence strategies used in both real and experimental settings.

8.
Biomedicines ; 11(5)2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37238956

RESUMO

Osteosarcopenia (OSP) is a geriatric syndrome characterized by the coexistence of osteoporosis and sarcopenia and associated with an increased risk of fragility fractures, disability, and mortality. For patients with this syndrome, musculoskeletal pain represents the most significant challenge since, in addition to limiting the individual's functionality and promoting disability, it has a huge psychological burden involving anxiety, depression, and social withdrawal. Unfortunately, the molecular mechanisms involved in the development and persistence of pain in OSP have not yet been fully elucidated, although immune cells are known to play a key role in these processes. Indeed, they release several molecules that promote persistent inflammation and nociceptive stimulation, resulting in the gating of ion channels responsible for the generation and propagation of the noxious stimulus. The adoption of countermeasures to counteract the OSP progression and reduce the algic component appears to be necessary, providing patients with a better quality of life and greater adherence to treatment. In addition, the development of multimodal therapies, based on an interdisciplinary approach, appears to be crucial, combining the use of anti-osteoporotic drugs with an educational programme, regular physical activity, and proper nutrition to eliminate risk factors. Based on this evidence, we conducted a narrative review using the PubMed and Google Scholar search engines to summarize the current knowledge on the molecular mechanisms involved in the pain development in OSP and the potential countermeasures to be taken. The lack of studies addressing this topic highlights the need to conduct new research into the resolution of an ever-expanding social problem.

9.
Front Physiol ; 14: 1107933, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37008023

RESUMO

Spaceflight exposure, like prolonged skeletal unloading, is known to result in significant bone loss, but the molecular mechanisms responsible are still partly unknown. This impairment, characterizing both conditions, suggests the possibility of identifying common signalling pathways and developing innovative treatment strategies to counteract the bone loss typical of astronauts and osteoporotic patients. In this context, primary cell cultures of human osteoblasts derived from healthy subjects and osteoporotic patients were exposed to random positioning machine (RPM) to reproduce the absence of gravity and to exacerbate the pathological condition, respectively. The duration of exposure to RPM was 3 or 6 days, with the aim of determining whether a single administration of recombinant irisin (r-irisin) could prevent cell death and mineralizing capacity loss. In detail, cellular responses were assessed both in terms of death/survival, by MTS assay, analysis of oxidative stress and caspase activity, as well as the expression of survival and cell death proteins, and in terms of mineralizing capacity, by investigating the pentraxin 3 (PTX3) expression. Our results suggest that the effects of a single dose of r-irisin are maintained for a limited time, as demonstrated by complete protection after 3 days of RPM exposure and only partial protection when RPM exposure was for a longer time. Therefore, the use of r-irisin could be a valid strategy to counteract the bone mass loss induced by weightlessness and osteoporosis. Further studies are needed to determine an optimal treatment strategy based on the use of r-irisin that is fully protective even over very long periods of exposure and/or to identify further approaches to be used in a complementary manner.

10.
Ther Adv Musculoskelet Dis ; 14: 1759720X221138354, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36465879

RESUMO

Osteosarcopenia (OS) is a newly defined condition represented by the simultaneous presence of osteopenia/osteoporosis and sarcopenia, the main age-related diseases. The simultaneous coexistence of the two phenotypes derives from the close connection of the main target tissues involved in their pathogenesis: bone and muscle. These two actors constitute the bone-muscle unit, which communicates through a biochemical and mechanical crosstalk which involves multiple factors. Altered pattern of molecular pathways leads to an impairment of both the functionality of the tissue itself and the communication with the complementary tissue, composing the OS pathogenesis. Recent advances in the genetics field have provided the opportunity to delve deeper into the complex biological and molecular mechanisms underlying OS. Unfortunately, there are still many gaps in our understanding of these pathways, but it has proven essential to apply strategies such as exercise and nutritional intervention to counteract OS. New therapeutic strategies that simultaneously target bone and muscle tissue are limited, but recently new targets for the development of dual-action drug therapies have been identified. This narrative review aims to provide an overview of the latest scientific evidence associated with OS, a complex disorder that will pave the way for future research aimed at understanding the bone-muscle-associated pathogenetic mechanisms.

11.
BMC Musculoskelet Disord ; 23(1): 1046, 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36457070

RESUMO

BACKGROUND: Osteoporosis is a complex multifactorial disease characterized by reduced bone mass and microarchitectural deterioration of bone tissue linked to an increase of fracture risk. Fragility fractures occur in osteoporotic subjects due to low-energy trauma. Osteoporotic patients are a challenge regarding the correct surgical planning, as it can include fixation augmentation techniques to reach a more stable anchorage of the implant, possibly lowering re-intervention rate and in-hospital stay. METHODS: The PubMed database and the Google Scholar search engine were used to identify articles on all augmentation techniques and their association with fragility fractures until January 2022. In total, we selected 40 articles that included studies focusing on humerus, hip, spine, and tibia. RESULTS: Literature review showed a quantity of materials that can be used for reconstruction of bone defects in fragility fractures in different anatomic locations, with good results over the stability and strength of the implant anchorage, when compared to non-augmented fractures. CONCLUSION: Nowadays there are no recommendations and no consensus about the use of augmentation techniques in osteoporotic fractures. Our literature review points at implementing the use of bone augmentation techniques with a specific indication for elderly patients with comminuted fractures and poor bone quality.


Assuntos
Fraturas Cominutivas , Osteoporose , Fraturas por Osteoporose , Idoso , Humanos , Osteoporose/complicações , Densidade Óssea , Fraturas por Osteoporose/cirurgia , Úmero
12.
Ther Adv Musculoskelet Dis ; 14: 1759720X221130485, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36317068

RESUMO

SARS-CoV-2 has caused a global pandemic and an unprecedented public health crisis, infecting more than 580 million people worldwide. Moreover, recent evidence has suggested the emergence of a new syndrome known as Long-COVID, a term used to describe a diverse set of physical and mental symptoms that persist after a diagnosed SARS-CoV-2 infection. Epidemiological data have identified myalgias, muscle and joint dysfunction, and bone fragility as common sequelae in patients with moderate and severe forms of this disease. Significant musculoskeletal dysfunction has also been detected in some healed patients, although knowledge about pathophysiological mechanisms of Long-COVID is still rather scarce. In this context, SARS-CoV-2 infection has been suggested to amplify the effects of aging on the musculoskeletal system by aggravating the osteosarcopenic state. Based on this evidence, our review focused on the muscle and bone tissue alterations induced by SARS-CoV-2 infection and Long-COVID, summarizing the current knowledge on the underlying biological mechanisms and highlighting the need for a multidisciplinary approach to predict the musculoskeletal targets and long-term consequences of COVID-19 disease.

13.
J Funct Morphol Kinesiol ; 7(4)2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36412761

RESUMO

Several studies agree that mechanical vibration can induce physiological changes at different levels, improving neuromuscular function through postural control strategies, muscle tuning mechanisms and tonic vibration reflexes. Whole-body vibration has also been reported to increase bone mineral density and muscle mass and strength, as well as to relieve pain and modulate proprioceptive function in patients with osteoarthritis or lower back pain. Furthermore, vibratory training was found to be an effective strategy for improving the physical performance of healthy athletes in terms of muscle strength, agility, flexibility, and vertical jump height. Notably, several benefits have also been observed at the brain level, proving to be an important factor in protecting and/or preventing the development of age-related cognitive disorders. Although research in this field is still debated, certain molecular mechanisms responsible for the response to whole-body vibration also appear to be involved in physiological adaptations to exercise, suggesting the possibility of using it as an alternative or reinforcing strategy to canonical training. Understanding these mechanisms is crucial for the development of whole body vibration protocols appropriately designed based on individual needs to optimize these effects. Therefore, we performed a narrative review of the literature, consulting the bibliographic databases MEDLINE and Google Scholar, to i) summarize the most recent scientific evidence on the effects of whole-body vibration and the molecular mechanisms proposed so far to provide a useful state of the art and ii) assess the potential of whole-body vibration as a form of passive training in place of or in association with exercise.

14.
Int J Mol Sci ; 23(18)2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36142305

RESUMO

Whole body vibration (WBV) is well known to exert beneficial effects on multiple tissues, improving synaptic transmission, muscle mass, bone quality, and reducing anxiety and depressive behavior. However, the underlying molecular mechanisms are not yet fully understood, and organs and tissues may respond differently to the vibratory stimulus depending on multiple factors. Therefore, we investigated the WBV effects on the brain and musculoskeletal tissue of 4-month-old young mice, evaluating synaptic plasticity by electrophysiological recordings and tissue organization by histology and histomorphometric analysis. Specifically, WBV protocols were characterized by the same vibration frequency (45 Hz), but different in vibration exposure time (five series of 3 min for the B protocol and three series of 2 min and 30 s for the C protocol) and recovery time between two vibration sessions (1 min for the B protocol and 2 min and 30 s for the C protocol). In addition, immunohistochemistry was conducted to evaluate the expression of fibronectin type III domain-containing protein 5 (FNDC5), as well as that of tissue-specific markers, such as brain-derived neurotrophic factor (BDNF) in brain, myostatin in muscle and collagen I (COL-1) in bone. Our results suggest that the WBV effects depend closely on the type of protocol used and support the hypothesis that different organs or tissues have different susceptibility to vibration. Further studies will be needed to deepen our knowledge of physiological adaptations to vibration and develop customized WBV protocols to improve and preserve cognitive and motor functions.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Vibração , Adaptação Fisiológica , Animais , Encéfalo , Colágeno , Fibronectinas , Camundongos , Miostatina , Vibração/uso terapêutico
15.
Osteoporos Int ; 33(12): 2467-2478, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35851407

RESUMO

Osteoporotic fractures are one of the major problems facing healthcare systems worldwide. Undoubtedly, fragility fractures of the hip represent a far greater burden in terms of morbidity, mortality, and healthcare costs than other fracture sites. However, despite the significant impact on the health and quality of life of older adults, there is a general lack of awareness of osteoporosis, which results in suboptimal care. In fact, most high-risk individuals are never identified and do not receive adequate treatment, leading to further fragility fractures and worsening health status. Furthermore, considering the substantial treatment gap and the proven cost-effectiveness of fracture prevention programs such as Fracture Liaison Services, urgent action is needed to ensure that all individuals at high risk of fragility fracture are adequately assessed and treated. Based on this evidence, the aim of our review was to (i) provide an overview and comparison of the burden and management of fragility fractures, highlighting the main gaps, and (ii) highlight the importance of using alternative approaches, both surgical and non-surgical, with the aim of implementing early prevention of osteoporotic fractures and improving the management of osteoporotic patients at imminent and/or very high risk of fracture.


Assuntos
Conservadores da Densidade Óssea , Osteoporose , Fraturas por Osteoporose , Humanos , Idoso , Fraturas por Osteoporose/prevenção & controle , Fraturas por Osteoporose/cirurgia , Qualidade de Vida , Osteoporose/complicações , Osteoporose/terapia , Análise Custo-Benefício , Atenção à Saúde , Prevenção Secundária , Conservadores da Densidade Óssea/uso terapêutico
16.
J Funct Morphol Kinesiol ; 7(2)2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35645300

RESUMO

Scientific evidence has demonstrated the power of physical exercise in the prevention and treatment of numerous chronic and/or age-related diseases, such as musculoskeletal, metabolic, and cardiovascular disorders. In addition, regular exercise is known to play a key role in the context of neurodegenerative diseases, as it helps to reduce the risk of their onset and counteracts their progression. However, the underlying molecular mechanisms have not yet been fully elucidated. In this regard, neurotrophins, such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), glia cell line-derived neurotrophic factor (GDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), have been suggested as key mediators of brain health benefits, as they are involved in neurogenesis, neuronal survival, and synaptic plasticity. The production of these neurotrophic factors, known to be increased by physical exercise, is downregulated in neurodegenerative disorders, suggesting their fundamental importance in maintaining brain health. However, the mechanism by which physical exercise promotes the production of neurotrophins remains to be understood, posing limits on their use for the development of potential therapeutic strategies for the treatment of neurodegenerative diseases. In this literature review, we analyzed the most recent evidence regarding the relationship between physical exercise, neurotrophins, and brain health, providing an overview of their involvement in the onset and progression of neurodegeneration.

17.
Life (Basel) ; 12(5)2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35629278

RESUMO

Bone loss is among the most frequent changes seen in astronauts during space missions. Although weightlessness is known to cause high bone resorption and a rapid decrease in bone minerals and calcium, the underlying mechanisms are not yet fully understood. In our work, we investigated the influence of random positioning machine (RPM) exposure on the mineralization process in the SAOS-2 cell line, in osteogenic and non-osteogenic conditions, by examining changes in their mineralizing capacity and in the expression of PTX3, a positive regulator of bone mineralization. We analyzed cell viability by MTS assay and the mineralization process after staining with Toluidine Blue and Alizarin Red, while PTX3 expression was investigated by immunocytochemistry and western blotting analysis. Our results showed that RPM exposure increased cells' viability and improved their mineralizing competence when not treated with osteogenic cocktail. In contrast, in osteogenic conditions, cells exposed to RPM showed a reduction in the presence of calcification-like structures, mineral deposits and PTX3 expression, suggesting that the effects of RPM exposure on mineralizing matrix deposition depend on the presence of osteogenic factors in the culture medium. Further studies will be needed to clarify the role of potential mineralization markers in the cellular response to the simulated biological effects of microgravity, paving the way for a new approach to treating osteoporosis in astronauts exposed to spaceflight.

18.
J Clin Med ; 11(9)2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35566735

RESUMO

Musculoskeletal pain is a condition that characterises several diseases and represents a constantly growing issue with enormous socio-economic burdens, highlighting the importance of developing treatment algorithms appropriate to the patient's needs and effective management strategies. Indeed, the algic condition must be assessed and treated independently of the underlying pathological process since it has an extremely negative impact on the emotional and psychic aspects of the individual, leading to isolation and depression. A full understanding of the pathophysiological mechanisms involved in nociceptive stimulation and central sensitization is an important step in improving approaches to musculoskeletal pain. In this context, the bidirectional relationship between immune cells and neurons involved in nociception could represent a key point in the understanding of these mechanisms. Therefore, we provide an updated overview of the magnitude of the musculoskeletal pain problem, in terms of prevalence and costs, and summarise the role of the most important molecular players involved in the development and maintenance of pain. Finally, based on the pathophysiological mechanisms, we propose a model, called the "musculoskeletal pain cycle", which could be a useful tool to counteract resignation to the algic condition and provide a starting point for developing a treatment algorithm for the patient with musculoskeletal pain.

19.
Genes (Basel) ; 13(4)2022 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-35456459

RESUMO

Clusterin (CLU) is a secreted heterodimeric glycoprotein expressed in all organism fluids as well as in the intracellular matrix that plays key roles in several pathological processes. Its recent involvement in muscle degeneration of osteoporotic patients led to investigation of the role of CLU in bone metabolism, given the biochemical and biomechanical crosstalk of the bone-muscle unit. Quantitative real time-polymerase chain reaction (qRT-PCR) analysis of CLU expression was performed in both osteoblasts and Peripheral Blood Mononuclear Cells (PBMCs) from osteoporotic patients (OP) and healthy individuals (CTR). Furthermore, immunohistochemical analysis on femoral head tissues and enzyme-linked immunosorbent assay (ELISA) in plasma samples were performed to investigate CLU expression pattern. Finally, genotyping of CLU rs11136000 polymorphism has also been performed by qRT-PCR assays to explore a possible association with CLU expression levels. Data obtained showed a significantly increased expression level of secreted CLU isoform in PBMCs and osteoblasts from OP patients. Immunohistochemical analysis confirms the increased expression of CLU in OP patients, both in osteocytes and osteoblasts, while plasma analysis reveals a statistically significant decrease of CLU levels. Unfortunately, no functional association between CLU expression levels and the presence of CLU rs11136000 polymorphism in OP patients was found. These data suggest a potential role played by CLU as a potential biomarker for the diagnosis and prognosis of OP progression.


Assuntos
Clusterina , Osteoporose , Biomarcadores/metabolismo , Clusterina/genética , Humanos , Leucócitos Mononucleares/metabolismo , Osteoporose/genética , Reação em Cadeia da Polimerase em Tempo Real
20.
Front Physiol ; 13: 782000, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35185612

RESUMO

Several scientific evidence have shown that exposure to microgravity has a significant impact on the health of the musculoskeletal system by altering the expression of proteins and molecules involved in bone-muscle crosstalk, which is also observed in the research of microgravity effect simulation. Among these, the expression pattern of myostatin appears to play a key role in both load-free muscle damage and the progression of age-related musculoskeletal disorders, such as osteoporosis and sarcopenia. Based on this evidence, we here investigated the efficacy of treatment with anti-myostatin (anti-MSTN) antibodies on primary cultures of human satellite cells exposed to 72 h of random positioning machine (RPM). Cell cultures were obtained from muscle biopsies taken from a total of 30 patients (controls, osteoarthritic, and osteoporotic) during hip arthroplasty. The Pax7 expression by immunofluorescence was carried out for the characterization of satellite cells. We then performed morphological evaluation by light microscopy and immunocytochemical analysis to assess myostatin expression. Our results showed that prolonged RPM exposure not only caused satellite cell death, but also induced changes in myostatin expression levels with group-dependent variations. Surprisingly, we observed that the use of anti-MSTN antibodies induced a significant increase in cell survival after RPM exposure under all experimental conditions. Noteworthy, we found that the negative effect of RPM exposure was counteracted by treatment with anti-MSTN antibodies, which allowed the formation of numerous myotubes. Our results highlight the role of myostatin as a major effector of the cellular degeneration observed with RPM exposure, suggesting it as a potential therapeutic target to slow the muscle mass loss that occurs in the absence of loading.

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