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1.
J Nanobiotechnology ; 22(1): 314, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38840113

RESUMO

Osteoporosis is the most common bone metabolic disease that affects the health of middle-aged and elderly people, which is hallmarked by imbalanced bone remodeling and a deteriorating immune microenvironment. Magnesium and calcium are pivotal matrix components that participate in the bone formation process, especially in the immune microenvironment regulation and bone remodeling stages. Nevertheless, how to potently deliver magnesium and calcium to bone tissue remains a challenge. Here, we have constructed a multifunctional nanoplatform composed of calcium-based upconversion nanoparticles and magnesium organic frameworks (CM-NH2-PAA-Ald, denoted as CMPA), which features bone-targeting and pH-responsive properties, effectively regulating the inflammatory microenvironment and promoting the coordination of osteogenic functions for treating osteoporosis. The nanoplatform can efficaciously target bone tissue and gradually degrade in response to the acidic microenvironment of osteoporosis to release magnesium and calcium ions. This study validates that CMPA possessing favorable biocompatibility can suppress inflammation and facilitate osteogenesis to treat osteoporosis. Importantly, high-throughput sequencing results demonstrate that the nanoplatform exerts a good inflammatory regulation effect through inhibition of the nuclear factor kappa-B signaling pathway, thereby normalizing the osteoporotic microenvironment. This collaborative therapeutic strategy that focuses on improving bone microenvironment and promoting osteogenesis provides new insight for the treatment of metabolic diseases such as osteoporosis.


Assuntos
Cálcio , Magnésio , Nanopartículas , Osteogênese , Osteoporose , Osteogênese/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Magnésio/farmacologia , Magnésio/química , Cálcio/metabolismo , Animais , Nanopartículas/química , Camundongos , Inflamação/tratamento farmacológico , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Humanos , Microambiente Celular/efeitos dos fármacos , Feminino , NF-kappa B/metabolismo
2.
Eur J Med Res ; 29(1): 317, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38849920

RESUMO

The brain-bone axis has emerged as a captivating field of research, unveiling the intricate bidirectional communication between the central nervous system (CNS) and skeletal metabolism. This comprehensive review delves into the current state of knowledge surrounding the brain-bone axis, exploring the complex mechanisms, key players, and potential clinical implications of this fascinating area of study. The review discusses the neural regulation of bone metabolism, highlighting the roles of the sympathetic nervous system, hypothalamic neuropeptides, and neurotransmitters in modulating bone remodeling. In addition, it examines the influence of bone-derived factors, such as osteocalcin and fibroblast growth factor 23, on brain function and behavior. The therapeutic potential of targeting the brain-bone axis in the context of skeletal and neurological disorders is also explored. By unraveling the complex interplay between the CNS and skeletal metabolism, this review aims to provide a comprehensive resource for researchers, clinicians, and students interested in the brain-bone axis and its implications for human health and disease.


Assuntos
Osso e Ossos , Encéfalo , Sistema Nervoso Central , Humanos , Osso e Ossos/metabolismo , Osso e Ossos/fisiologia , Encéfalo/metabolismo , Encéfalo/fisiologia , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/fisiologia , Animais , Remodelação Óssea/fisiologia , Sistema Nervoso Simpático/fisiologia , Sistema Nervoso Simpático/metabolismo
4.
Sci Transl Med ; 16(750): eadk9811, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38838134

RESUMO

Clinical evidence indicates a close association between muscle dysfunction and bone loss; however, the underlying mechanisms remain unclear. Here, we report that muscle dysfunction-related bone loss in humans with limb-girdle muscular dystrophy is associated with decreased expression of folliculin-interacting protein 1 (FNIP1) in muscle tissue. Supporting this finding, murine gain- and loss-of-function genetic models demonstrated that muscle-specific ablation of FNIP1 caused decreased bone mass, increased osteoclastic activity, and mechanical impairment that could be rescued by myofiber-specific expression of FNIP1. Myofiber-specific FNIP1 deficiency stimulated expression of nuclear translocation of transcription factor EB, thereby activating transcription of insulin-like growth factor 2 (Igf2) at a conserved promoter-binding site and subsequent IGF2 secretion. Muscle-derived IGF2 stimulated osteoclastogenesis through IGF2 receptor signaling. AAV9-mediated overexpression of IGF2 was sufficient to decrease bone volume and impair bone mechanical properties in mice. Further, we found that serum IGF2 concentration was negatively correlated with bone health in humans in the context of osteoporosis. Our findings elucidate a muscle-bone cross-talk mechanism bridging the gap between muscle dysfunction and bone loss. This cross-talk represents a potential target to treat musculoskeletal diseases and osteoporosis.


Assuntos
Osso e Ossos , Fator de Crescimento Insulin-Like II , Animais , Fator de Crescimento Insulin-Like II/metabolismo , Humanos , Osso e Ossos/metabolismo , Camundongos , Transdução de Sinais , Músculo Esquelético/metabolismo , Osteogênese , Músculos/metabolismo , Masculino , Feminino , Osteoclastos/metabolismo
5.
Food Res Int ; 188: 114513, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38823886

RESUMO

This study reports the effect of thermal pretreatment and the use of different commercial proteolytic enzymes (Protamex, Flavourzyme, Protana prime, and Alcalase) on the free amino acid content (FAA), peptide profile, and antioxidant, antidiabetic, antihypertensive, and anti-inflammatory potential (DPPH, FRAP, and ABTS assay, DPP-IV, ACE-I, and NEP inhibitory activities) of dry-cured ham bone hydrolyzates. The effect of in vitro digestion was also determined. Thermal pretreatment significantly increased the degree of hydrolysis, the FAA, and the DPP-IV and ACE-I inhibitory activities. The type of peptidase used was the most significant factor influencing antioxidant activity and neprilysin inhibitory activity. Protana prime hydrolyzates failed to inhibit DPP-IV and neprilysin enzymes and had low values of ACE-I inhibitory activity. After in vitro digestion, bioactivities kept constant in most cases or even increased in ACE-I inhibitory activity. Therefore, hydrolyzates from dry-cured ham bones could serve as a potential source of functional food ingredients for health benefits.


Assuntos
Antioxidantes , Digestão , Animais , Hidrólise , Antioxidantes/metabolismo , Antioxidantes/análise , Osso e Ossos/metabolismo , Suínos , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/metabolismo , Manipulação de Alimentos/métodos , Temperatura Alta , Aminoácidos/metabolismo , Aminoácidos/análise , Produtos da Carne/análise , Hipoglicemiantes/farmacologia , Anti-Hipertensivos/farmacologia , Anti-Inflamatórios/farmacologia , Peptídeo Hidrolases/metabolismo , Inibidores da Dipeptidil Peptidase IV , Neprilisina/metabolismo , Neprilisina/antagonistas & inibidores , Endopeptidases
6.
Cell Mol Biol (Noisy-le-grand) ; 70(6): 61-65, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38836683

RESUMO

This experiment aimed to explore the influence mechanism of external fixator on open fracture. A total of 128 patients with open tibiofibular fractures were included in this study. The patients were randomly divided into external fixator group (n=64) and control group (n=64) according to the order of admission. Double-blind controlled observation was used. The levels of osteocalcin (BGP), ß-CTX, P1 NP, BALP, including haptoglobin (Hp), ceruloplasmin (CER), serum adrenocorticotropic hormone (ACTH), cortisol (COR), C-reactive protein (CRP), white blood cell (WBC) and interleukin-6 (IL-6) were recorded in different groups. The postoperative VAS score and quality of life were recorded. Log-rank was used to analyze the difference in postoperative adverse reaction rates among different groups. External fixation stent treatment increased BGP, PINP, and BALP expression and decreased ß-CTX, Hp, CER, ACTH, COR, CRP, WBC, and IL-6 levels. Patients in the external fixation stent group had significantly lower VAS score quality of life scores and incidence of adverse events than the control group. External fixation stents protect open fracture patients by promoting bone metabolism.


Assuntos
Osso e Ossos , Proteína C-Reativa , Fixadores Externos , Osteocalcina , Qualidade de Vida , Humanos , Masculino , Feminino , Adulto , Osteocalcina/sangue , Osteocalcina/metabolismo , Pessoa de Meia-Idade , Osso e Ossos/metabolismo , Proteína C-Reativa/metabolismo , Fraturas Expostas/cirurgia , Fraturas Expostas/metabolismo , Interleucina-6/sangue , Interleucina-6/metabolismo , Pró-Colágeno/sangue , Pró-Colágeno/metabolismo , Método Duplo-Cego , Colágeno Tipo I/metabolismo , Colágeno Tipo I/sangue , Hormônio Adrenocorticotrópico/sangue , Hormônio Adrenocorticotrópico/metabolismo , Fragmentos de Peptídeos/sangue , Extremidades/cirurgia , Extremidades/lesões , Peptídeos , Hidrocortisona/sangue
7.
Heart Fail Clin ; 20(3): 307-316, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38844301

RESUMO

Cardiac amyloidosis (CA) is caused by the myocardial deposition of misfolded proteins, either amyloid transthyretin (ATTR) or immunoglobulin light chains (AL). The paradigm of this condition has transformed, since CA is increasingly recognized as a relatively prevalent cause of heart failure. Cardiac scintigraphy with bone tracers is the unique noninvasive technique able to confirm CA without performing tissue biopsy or advanced imaging tests. A moderate-to-intense myocardial uptake (Perugini grade ≥2) associated with the absence of a monoclonal component is greater than 99% specific for ATTR-CA, while AL-CA confirmation requires tissue biopsy.


Assuntos
Amiloidose , Cardiomiopatias , Compostos Radiofarmacêuticos , Humanos , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/metabolismo , Amiloidose/diagnóstico por imagem , Amiloidose/metabolismo , Amiloidose/patologia , Cintilografia/métodos , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Miocárdio/patologia , Miocárdio/metabolismo , Neuropatias Amiloides Familiares/diagnóstico por imagem , Neuropatias Amiloides Familiares/metabolismo , Neuropatias Amiloides Familiares/patologia , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/metabolismo , Pré-Albumina/metabolismo
8.
FASEB J ; 38(11): e23726, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38847773

RESUMO

Calcitriol and calcimimetics are used to treat hyperparathyroidism secondary to chronic kidney disease (CKD). Calcitriol administration and the subsequent increase in serum calcium concentration decrease parathyroid hormone (PTH) levels, which should reduce bone remodeling. We have previously reported that, when maintaining a given concentration of PTH, the addition of calcimimetics is associated with an increased bone cell activity. Whether calcitriol administration affects bone cell activity while PTH is maintained constant should be evaluated in an animal model of renal osteodystrophy. The aim of the present study was to compare in CKD PTH-clamped rats the bone effects of calcitriol and calcimimetic administration. The results show that the administration of calcitriol and calcimimetic at doses that induced a similar reduction in PTH secretion produced dissimilar effects on osteoblast activity in 5/6 nephrectomized (Nx) rats with secondary hyperparathyroidism and in Nx rats with clamped PTH. Remarkably, in both rat models, the administration of calcitriol decreased osteoblastic activity, whereas calcimimetic increased bone cell activity. In vitro, calcitriol supplementation inhibited nuclear translocation of ß-catenin and reduced proliferation, osteogenesis, and mineralization in mesenchymal stem cells differentiated into osteoblasts. In conclusion, besides the action of calcitriol and calcimimetics at parathyroid level, these treatments have specific effects on bone cells that are independent of the PTH level.


Assuntos
Calcimiméticos , Calcitriol , Osteoblastos , Hormônio Paratireóideo , Animais , Calcitriol/farmacologia , Ratos , Calcimiméticos/farmacologia , Calcimiméticos/uso terapêutico , Hormônio Paratireóideo/farmacologia , Masculino , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Hiperparatireoidismo Secundário/tratamento farmacológico , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/metabolismo , Osso e Ossos/metabolismo , Osso e Ossos/efeitos dos fármacos , Ratos Wistar , Insuficiência Renal/tratamento farmacológico , Insuficiência Renal/metabolismo , Osteogênese/efeitos dos fármacos , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/complicações , Diferenciação Celular/efeitos dos fármacos , Cálcio/metabolismo
9.
FASEB J ; 38(9): e23642, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38690719

RESUMO

Alterations to the human organism that are brought about by aging are comprehensive and detrimental. Of these, an imbalance in bone homeostasis is a major outward manifestation of aging. In older adults, the decreased osteogenic activity of bone marrow mesenchymal stem cells and the inhibition of bone marrow mesenchymal stem cell differentiation lead to decreased bone mass, increased risk of fracture, and impaired bone injury healing. In the past decades, numerous studies have reported the epigenetic alterations that occur during aging, such as decreased core histones, altered DNA methylation patterns, and abnormalities in noncoding RNAs, which ultimately lead to genomic abnormalities and affect the expression of downstream signaling osteoporosis treatment and promoter of fracture healing in older adults. The current review summarizes the impact of epigenetic regulation mechanisms on age-related bone homeostasis imbalance.


Assuntos
Envelhecimento , Osso e Ossos , Epigênese Genética , Homeostase , Humanos , Envelhecimento/genética , Envelhecimento/fisiologia , Animais , Osso e Ossos/metabolismo , Metilação de DNA , Osteoporose/genética , Osteoporose/metabolismo , Células-Tronco Mesenquimais/metabolismo , Osteogênese/genética , Osteogênese/fisiologia , Histonas/metabolismo
10.
Front Endocrinol (Lausanne) ; 15: 1301213, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38742199

RESUMO

Purpose: To investigate the relationship between bone turnover markers (BTMs) and thyroid indicators in Graves' disease (GD) and to further assess predictive value of changes in early stage retrospectively. Methods: We studied 435 patients with GD and 113 healthy physical examiners retrospectively and followed up these two groups of patients after 6 months. We investigated the correlations between BTMs and other 15 observed factors, and analyzed the predictive value of FT3 and FT4 before and after treatment (FT3-P/FT3-A, FT4-P/FT4-A) on whether BTMs recovered. Results: The levels of thyroid hormones and BTMs in GD group were significantly higher than those in control group (P < 0.05) and decreased after 6 months of treatment. FT3, W, Ca and ALP were independent factors in predicting the elevation of OST. Duration of disease, FT3, TSH and ALP were independent factors in predicting the elevation of P1NP. Age, duration of disease, TRAb and ALP were independent factors in predicting the elevation of CTX-1. The AUC of FT3-P/FT3-A and FT4-P/FT4-A for predicting OST recovery were 0.748 and 0.705 (P < 0.05), respectively, and the cut-off values were 0.51 and 0.595. There was no predictive value for P1NP and CTX-1 recovery (P > 0.05). Conclusion: BTMs were abnormally elevated in GD and were significantly correlated with serum levels of FT3, FT4, TRAb, Ca, and ALP. FT3 decreased more than 51% and FT4 dropped more than 59.5% after 6 months of treatment were independent predictors for the recovery of BTMs in GD.


Assuntos
Biomarcadores , Remodelação Óssea , Doença de Graves , Valor Preditivo dos Testes , Humanos , Masculino , Feminino , Doença de Graves/sangue , Doença de Graves/tratamento farmacológico , Doença de Graves/metabolismo , Adulto , Biomarcadores/sangue , Estudos Retrospectivos , Pessoa de Meia-Idade , Glândula Tireoide/metabolismo , Osso e Ossos/metabolismo , Hormônios Tireóideos/sangue , Estudos de Casos e Controles , Prognóstico , Antitireóideos/uso terapêutico , Tiroxina/sangue , Tri-Iodotironina/sangue , Seguimentos
11.
J Bras Nefrol ; 46(3): e20240023, 2024.
Artigo em Inglês, Português | MEDLINE | ID: mdl-38748946

RESUMO

In the last few years, evidence from the Brazilian Registry of Bone Biopsy (REBRABO) has pointed out a high incidence of aluminum (Al) accumulation in the bones of patients with CKD under dialysis. This surprising finding does not appear to be merely a passive metal accumulation, as prospective data from REBRABO suggest that the presence of Al in bone may be independently associated with major adverse cardiovascular events. This information contrasts with the perception of epidemiologic control of this condition around the world. In this opinion paper, we discussed why the diagnosis of Al accumulation in bone is not reported in other parts of the world. We also discuss a range of possibilities to understand why bone Al accumulation still occurs, not as a classical syndrome with systemic signs of intoxication, as occurred it has in the past.


Assuntos
Alumínio , Osso e Ossos , Humanos , Alumínio/metabolismo , Alumínio/efeitos adversos , Osso e Ossos/metabolismo , Diálise Renal , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/complicações , Brasil/epidemiologia
12.
Sci Rep ; 14(1): 10888, 2024 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740835

RESUMO

Ethylenediaminetetraacetic acid (EDTA), a classically used chelating agent of decalcification, maintains good morphological details, but its slow decalcification limits its wider applications. Many procedures have been reported to accelerate EDTA-based decalcification, involving temperature, concentration, sonication, agitation, vacuum, microwave, or combination. However, these procedures, concentrating on purely tissue-outside physical factors to increase the chemical diffusion, do not enable EDTA to exert its full capacity due to tissue intrinsic chemical resistances around the diffusion passage. The resistances, such as tissue inner lipids and electric charges, impede the penetration of EDTA. We hypothesized that delipidation and shielding electric charges would accelerate EDTA-based penetration and the subsequent decalcification. The hypothesis was verified by the observation of speedy penetration of EDTA with additives of detergents and hypertonic saline, testing on tissue-mimicking gels of collagen and adult mouse bones. Using a 26% EDTA mixture with the additives at 45°C, a conventional 7-day decalcification of adult mouse ankle joints could be completed within 24 h while the tissue morphological structure, antigenicity, enzymes, and DNA were well preserved, and mRNA better retained compared to using 15% EDTA at room temperature. The addition of hypertonic saline and detergents to EDTA decalcification is a simple, rapid, and inexpensive method that doesn't disrupt the current histological workflow. This method is equally or even more effective than the currently most used decalcification methods in preserving the morphological details of tissues. It can be highly beneficial for the related community.


Assuntos
Detergentes , Ácido Edético , RNA Mensageiro , Animais , Ácido Edético/química , Ácido Edético/farmacologia , Detergentes/química , Camundongos , RNA Mensageiro/genética , Solução Salina Hipertônica/química , Osso e Ossos/metabolismo , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/química , Técnica de Descalcificação/métodos
13.
Zhongguo Gu Shang ; 37(5): 519-26, 2024 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-38778538

RESUMO

OBJECTIVE: To explore the molecular mechanism of chronic osteomyelitis and to clarify the role of MAPK signal pathway in the pathogenesis of chronic osteomyelitis, by collecting and analyzing the transcriptional information of bone tissue in patients with chronic osteomyelitis. METHODS: Four cases of traumatic osteomyelitis in limbs from June 2019 to June 2020 were selected, and the samples of necrotic osteonecrosis from chronic osteomyelitis (necrotic group), and normal bone tissue (control group) were collected. Transcriptome information was collected by Illumina Hiseq Xten high throughput sequencing platform, and the gene expression in bone tissue was calculated by FPKM. The differentially expressed genes were screened by comparing the transcripts of the Necrotic group and control group. Genes were enriched by GO and KEGG. MAP3K7 and NFATC1 were selected as differential targets in the verification experiments, by using rat osteomyelitis animal model and immunohistochemical analysis. RESULTS: A total of 5548 differentially expressed genes were obtained by high throughput sequencing by comparing the necrotic group and control group, including 2701 up-regulated and 2847 down-regulated genes. The genes enriched in MAPK pathway and osteoclast differentiation pathway were screened, the common genes expressed in both MAPK and osteoclast differentiation pathway were (inhibitor of nuclear factor κ subunit Beta, IκBKß), (mitogen-activated protein kinase 7, MAP3K7), (nuclear factor of activated t cells 1, NFATC1) and (nuclear factor Kappa B subunit 2, NFκB2). In rat osteomyelitis model, MAP3K7 and NFATC1 were highly expressed in bone marrow and injured bone tissue. CONCLUSION: Based on the transcriptome analysis, the MAPK signaling and osteoclast differentiation pathways were closely related to chronic osteomyelitis, and the key genes IκBKß, MAP3K7, NFATC1, NFκB2 might be new targets for clinical diagnosis and therapy of chronic osteomyelitis.


Assuntos
Osteomielite , Transcriptoma , Osteomielite/genética , Animais , Humanos , Doença Crônica , Masculino , Ratos , Fatores de Transcrição NFATC/genética , Fatores de Transcrição NFATC/metabolismo , Perfilação da Expressão Gênica , Osso e Ossos/metabolismo , Ratos Sprague-Dawley , Feminino , Sistema de Sinalização das MAP Quinases/genética
14.
J Vis Exp ; (207)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38767376

RESUMO

Understanding the relationship between the cells and their location within each tissue is critical to uncover the biological processes associated with normal development and disease pathology. Spatial transcriptomics is a powerful method that enables the analysis of the whole transcriptome within tissue samples, thus providing information about the cellular gene expression and the histological context in which the cells reside. While this method has been extensively utilized for many soft tissues, its application for the analyses of hard tissues such as bone has been challenging. The major challenge resides in the inability to preserve good quality RNA and tissue morphology while processing the hard tissue samples for sectioning. Therefore, a method is described here to process freshly obtained bone tissue samples to effectively generate spatial transcriptomics data. The method allows for the decalcification of the samples, granting successful tissue sections with preserved morphological details while avoiding RNA degradation. In addition, detailed guidelines are provided for samples that were previously paraffin-embedded, without demineralization, such as samples collected from tissue banks. Using these guidelines, high-quality spatial transcriptomics data generated from tissue bank samples of primary tumor and lung metastasis of bone osteosarcoma are shown.


Assuntos
Neoplasias Ósseas , Osso e Ossos , Transcriptoma , Humanos , Transcriptoma/genética , Osso e Ossos/metabolismo , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Neoplasias Ósseas/metabolismo , Osteossarcoma/genética , Osteossarcoma/patologia , Osteossarcoma/metabolismo , Perfilação da Expressão Gênica/métodos , Inclusão em Parafina/métodos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo
15.
Biomolecules ; 14(5)2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38785961

RESUMO

Osteoporosis (OP), a prevalent skeletal disorder characterized by compromised bone strength and increased susceptibility to fractures, poses a significant public health concern. This review aims to provide a comprehensive analysis of the current state of research in the field, focusing on the application of proteomic techniques to elucidate diagnostic markers and therapeutic targets for OP. The integration of cutting-edge proteomic technologies has enabled the identification and quantification of proteins associated with bone metabolism, leading to a deeper understanding of the molecular mechanisms underlying OP. In this review, we systematically examine recent advancements in proteomic studies related to OP, emphasizing the identification of potential biomarkers for OP diagnosis and the discovery of novel therapeutic targets. Additionally, we discuss the challenges and future directions in the field, highlighting the potential impact of proteomic research in transforming the landscape of OP diagnosis and treatment.


Assuntos
Biomarcadores , Osteoporose , Proteômica , Humanos , Proteômica/métodos , Osteoporose/diagnóstico , Osteoporose/metabolismo , Osteoporose/tratamento farmacológico , Osteoporose/terapia , Biomarcadores/metabolismo , Doenças Ósseas Metabólicas/diagnóstico , Doenças Ósseas Metabólicas/metabolismo , Animais , Osso e Ossos/metabolismo
16.
Biomolecules ; 14(5)2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38785972

RESUMO

Background: Erectile dysfunction (ED) stands out as one of the most prevalent sexual disorders in men, with its incidence progressively escalating with age. As delineated by the International Consultation Committee for Sexual Medicine on Definitions/Epidemiology/Risk Factors for Sexual Dysfunction, the prevalence of ED among men under 40 years is estimated to be within the range of 1-10%. The aim of this study was to determine the relationship between the concentration of bioelements (Zn, Cu, Fe, Cr, Mg, and Mn) in the serum and bone tissue and the concentration of selected hormones in men with and without erectile dysfunction. Materials and methods: The retrospective cohort study included 152 men who underwent total hip arthroplasty for hip osteoarthritis at the Department of Orthopaedic Traumatology and Musculoskeletal Oncology at the Pomeranian Medical University in Szczecin. Certain exclusion criteria were applied to ensure the integrity of the study. These included individuals with diabetes, a history of cancer, alcohol abuse, liver or kidney failure, New York Heart Association (NYHA) class III or IV heart failure, and those taking medications that affect bone metabolism, such as mineral supplements, neuroleptics, chemotherapeutic agents, immunosuppressants, corticosteroids, or antidepressants. Patients with hypogonadism or infertility were excluded from the study. Results: The study showed an association between bioT concentrations and Cu concentrations in both patients with and without erectile dysfunction. A correlation between bioactive testosterone and Cr concentrations was also observed in both groups. Patients with erectile dysfunction showed a relationship between bioT concentration and Zn concentration, TT concentration and Mn concentration, FT concentration and Zn concentration, and E2 concentration and Cr concentration. An analysis of elemental concentrations in bone tissue showed an association between FT and Mg and Mn concentrations, but only in patients with erectile dysfunction. In patients without erectile dysfunction, a correlation was observed between FT and Cu concentrations. A correlation was also observed between bioT concentrations and Mg, Mn, and Zn concentrations, but only in patients with erectile dysfunction. In patients without erectile dysfunction, a correlation was observed between bioT and Cu concentrations. Conclusions: Studying the relationship between the concentration of bioelements (Zn, Cu, Fe, Cr, Mg, and Mn) in the serum and bone tissue and the concentration of selected hormones in men may be important in explaining the etiology of the problem. The study of the concentration of Zn and Cu in bone tissue and serum showed that these two elements, regardless of the place of accumulation, may be related to the concentration of androgens in men.


Assuntos
Artroplastia de Quadril , Osso e Ossos , Cobre , Disfunção Erétil , Zinco , Humanos , Masculino , Disfunção Erétil/sangue , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Zinco/sangue , Osso e Ossos/metabolismo , Cobre/sangue , Envelhecimento/sangue , Cromo/sangue , Magnésio/sangue , Ferro/sangue , Ferro/metabolismo , Manganês/sangue , Manganês/análise , Oligoelementos/sangue , Testosterona/sangue , Adulto
17.
Biomolecules ; 14(5)2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38785963

RESUMO

Bones are vital for anchoring muscles, tendons, and ligaments, serving as a fundamental element of the human skeletal structure. However, our understanding of bone development mechanisms and the maintenance of bone homeostasis is still limited. Extracellular signal-related kinase 5 (ERK5), a recently identified member of the mitogen-activated protein kinase (MAPK) family, plays a critical role in the pathogenesis and progression of various diseases, especially neoplasms. Recent studies have highlighted ERK5's significant role in both bone development and bone-associated pathologies. This review offers a detailed examination of the latest research on ERK5 in different tissues and diseases, with a particular focus on its implications for bone health. It also examines therapeutic strategies and future research avenues targeting ERK5.


Assuntos
Osso e Ossos , Proteína Quinase 7 Ativada por Mitógeno , Humanos , Proteína Quinase 7 Ativada por Mitógeno/metabolismo , Osso e Ossos/metabolismo , Osso e Ossos/enzimologia , Animais
18.
Mar Drugs ; 22(5)2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38786592

RESUMO

Malnutrition is one of the major factors of bone and cartilage disorders. Pacific cod (Gadus macrocephalus) processing waste is a cheap and highly promising source of bioactive substances, including collagen-derived peptides and amino acids, for bone and cartilage structure stabilization. The addition of these substances to a functional drink is one of the ways to achieve their fast intestinal absorption. Collagen hydrolysate was obtained via enzymatic hydrolysis, ultrafiltration, freeze-drying, and grinding to powder. The lyophilized hydrolysate was a light gray powder with high protein content (>90%), including collagen (about 85% of total protein) and a complete set of essential and non-essential amino acids. The hydrolysate had no observed adverse effect on human mesenchymal stem cell morphology, viability, or proliferation. The hydrolysate was applicable as a protein food supply or a structure-forming food component due to the presence of collagen fiber fragments. An isotonic fitness drink (osmolality 298.1 ± 2.1 mOsm/L) containing hydrolysate and vitamin C as a cofactor in collagen biosynthesis was prepared. The addition of the hydrolysate did not adversely affect its organoleptic parameters. The production of such functional foods and drinks is one of the beneficial ways of fish processing waste utilization.


Assuntos
Osso e Ossos , Cartilagem , Colágeno , Gadiformes , Hidrolisados de Proteína , Animais , Colágeno/metabolismo , Humanos , Cartilagem/efeitos dos fármacos , Cartilagem/metabolismo , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Hidrolisados de Proteína/farmacologia , Hidrolisados de Proteína/química , Células-Tronco Mesenquimais/efeitos dos fármacos , Bebidas , Alimento Funcional , Hidrólise
19.
Int J Mol Sci ; 25(10)2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38791156

RESUMO

The deterioration of osteoblast-led bone formation and the upregulation of osteoclast-regulated bone resorption are the primary causes of bone diseases, including osteoporosis. Numerous circulating factors play a role in bone homeostasis by regulating osteoblast and osteoclast activity, including the sphingolipid-sphingosine-1-phosphate (S1P). However, to date no comprehensive studies have investigated the impact of S1P activity on human and murine osteoblasts and osteoclasts. We observed species-specific responses to S1P in both osteoblasts and osteoclasts, where S1P stimulated human osteoblast mineralisation and reduced human pre-osteoclast differentiation and mineral resorption, thereby favouring bone formation. The opposite was true for murine osteoblasts and osteoclasts, resulting in more mineral resorption and less mineral deposition. Species-specific differences in osteoblast responses to S1P were potentially explained by differential expression of S1P receptor 1. By contrast, human and murine osteoclasts expressed comparable levels of S1P receptors but showed differential expression patterns of the two sphingosine kinase enzymes responsible for S1P production. Ultimately, we reveal that murine models may not accurately represent how human bone cells will respond to S1P, and thus are not a suitable model for exploring S1P physiology or potential therapeutic agents.


Assuntos
Diferenciação Celular , Lisofosfolipídeos , Osteoblastos , Osteoclastos , Especificidade da Espécie , Esfingosina , Esfingosina/análogos & derivados , Esfingosina/metabolismo , Lisofosfolipídeos/metabolismo , Humanos , Animais , Camundongos , Osteoclastos/metabolismo , Osteoclastos/citologia , Osteoblastos/metabolismo , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Receptores de Esfingosina-1-Fosfato/metabolismo , Osso e Ossos/metabolismo , Reabsorção Óssea/metabolismo , Células Cultivadas
20.
Int J Mol Sci ; 25(10)2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38791243

RESUMO

Bone is a metabolically dynamic structure that is generally remodeled throughout the lifetime of an individual but often causes problems with increasing age. A key player for bone development and homeostasis, but also under pathological conditions, is the bone vasculature. This complex system of arteries, veins, and capillaries forms distinct structures where each subset of endothelial cells has important functions. Starting with the basic process of angiogenesis and bone-specific blood vessel formation, coupled with initial bone formation, the importance of different vascular structures is highlighted with respect to how these structures are maintained or changed during homeostasis, aging, and pathological conditions. After exemplifying the current knowledge on bone vasculature, this review will move on to exosomes, a novel hotspot of scientific research. Exosomes will be introduced starting from their discovery via current isolation procedures and state-of-the-art characterization to their role in bone vascular development, homeostasis, and bone regeneration and repair while summarizing the underlying signal transduction pathways. With respect to their role in these processes, especially mesenchymal stem cell-derived extracellular vesicles are of interest, which leads to a discussion on patented applications and an update on ongoing clinical trials. Taken together, this review provides an overview of bone vasculature and bone regeneration, with a major focus on how exosomes influence this intricate system, as they might be useful for therapeutic purposes in the near future.


Assuntos
Regeneração Óssea , Exossomos , Neovascularização Fisiológica , Humanos , Exossomos/metabolismo , Animais , Osso e Ossos/metabolismo , Osso e Ossos/irrigação sanguínea , Células-Tronco Mesenquimais/metabolismo , Osteogênese , Transdução de Sinais , Células Endoteliais/metabolismo , Angiogênese
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