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1.
Int J Mol Sci ; 22(6)2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33802713

RESUMO

Spinal cord injury (SCI) affects approximately 300,000 people in the United States. Most individuals who sustain severe SCI also develop subsequent osteoporosis. However, beyond immobilization-related lack of long bone loading, multiple mechanisms of SCI-related bone density loss are incompletely understood. Recent findings suggest neuronal impairment and disability may lead to an upregulation of receptor activator of nuclear factor-κB ligand (RANKL), which promotes bone resorption. Disruption of Wnt signaling and dysregulation of RANKL may also contribute to the pathogenesis of SCI-related osteoporosis. Estrogenic effects may protect bones from resorption by decreasing the upregulation of RANKL. This review will discuss the current proposed physiological and cellular mechanisms explaining osteoporosis associated with SCI. In addition, we will discuss emerging pharmacological and physiological treatment strategies, including the promising effects of estrogen on cellular protection.


Assuntos
Osteoporose/etiologia , Osteoporose/fisiopatologia , Traumatismos da Medula Espinal/complicações , Animais , Remodelação Óssea/fisiologia , Estrogênios/uso terapêutico , Exercício Físico , Humanos , Osteoporose/tratamento farmacológico , Transdução de Sinais
2.
Molecules ; 26(6)2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33805847

RESUMO

Autologous bone grafts, used mainly in extensive bone loss, are considered the gold standard treatment in regenerative medicine, but still have limitations mainly in relation to the amount of bone available, donor area, morbidity and creation of additional surgical area. This fact encourages tissue engineering in relation to the need to develop new biomaterials, from sources other than the individual himself. Therefore, the present study aimed to investigate the effects of an elastin and collagen matrix on the bone repair process in critical size defects in rat calvaria. The animals (Wistar rats, n = 30) were submitted to a surgical procedure to create the bone defect and were divided into three groups: Control Group (CG, n = 10), defects filled with blood clot; E24/37 Group (E24/37, n = 10), defects filled with bovine elastin matrix hydrolyzed for 24 h at 37 °C and C24/25 Group (C24/25, n = 10), defects filled with porcine collagen matrix hydrolyzed for 24 h at 25 °C. Macroscopic and radiographic analyses demonstrated the absence of inflammatory signs and infection. Microtomographical 2D and 3D images showed centripetal bone growth and restricted margins of the bone defect. Histologically, the images confirmed the pattern of bone deposition at the margins of the remaining bone and without complete closure by bone tissue. In the morphometric analysis, the groups E24/37 and C24/25 (13.68 ± 1.44; 53.20 ± 4.47, respectively) showed statistically significant differences in relation to the CG (5.86 ± 2.87). It was concluded that the matrices used as scaffolds are biocompatible and increase the formation of new bone in a critical size defect, with greater formation in the polymer derived from the intestinal serous layer of porcine origin (C24/25).


Assuntos
Biopolímeros/química , Regeneração Óssea/fisiologia , Tecidos Suporte/química , Animais , Materiais Biocompatíveis/química , Birrefringência , Matriz Óssea/química , Matriz Óssea/fisiologia , Remodelação Óssea/fisiologia , Substitutos Ósseos/química , Calcificação Fisiológica/fisiologia , Bovinos , Colágeno/química , Colágeno/metabolismo , Elastina/química , Elastina/metabolismo , Imageamento Tridimensional , Masculino , Teste de Materiais , Ratos , Ratos Wistar , Crânio/diagnóstico por imagem , Crânio/lesões , Crânio/fisiologia , Suínos , Engenharia Tecidual/métodos , Microtomografia por Raio-X
3.
Int J Mol Sci ; 22(5)2021 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-33800057

RESUMO

Osteoarthritis (OA) is currently the most widespread musculoskeletal condition and primarily affects weight-bearing joints such as the knees and hips. Importantly, knee OA remains a multifactorial whole-joint disease, the appearance and progression of which involves the alteration of articular cartilage as well as the synovium, subchondral bone, ligaments, and muscles through intricate pathomechanisms. Whereas it was initially depicted as a predominantly aging-related and mechanically driven condition given its clear association with old age, high body mass index (BMI), and joint malalignment, more recent research identified and described a plethora of further factors contributing to knee OA pathogenesis. However, the pathogenic intricacies between the molecular pathways involved in OA prompted the study of certain drugs for more than one therapeutic target (amelioration of cartilage and bone changes, and synovial inflammation). Most clinical studies regarding knee OA focus mainly on improvement in pain and joint function and thus do not provide sufficient evidence on the possible disease-modifying properties of the tested drugs. Currently, there is an unmet need for further research regarding OA pathogenesis as well as the introduction and exhaustive testing of potential disease-modifying pharmacotherapies in order to structure an effective treatment plan for these patients.


Assuntos
Osteoartrite do Joelho/fisiopatologia , Osteoartrite do Joelho/terapia , Proteínas ADAMTS/antagonistas & inibidores , Animais , Produtos Biológicos/farmacologia , Remodelação Óssea/efeitos dos fármacos , Remodelação Óssea/fisiologia , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/fisiopatologia , Catepsina K/antagonistas & inibidores , Dieta , Exercício Físico/fisiologia , Humanos , Inibidores de Metaloproteinases de Matriz/farmacologia , Transplante de Células-Tronco Mesenquimais , Osteoartrite do Joelho/tratamento farmacológico , Plasma Rico em Plaquetas , Sinovite/tratamento farmacológico , Sinovite/etiologia , Proteínas Wnt/antagonistas & inibidores
4.
Nutrients ; 13(3)2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33671093

RESUMO

Suppression of insulin-like growth factor 1 (IGF-1) and leptin secondary to low energy availability (LEA) may contribute to adverse effects on bone health. Whether a high-protein diet attenuates these effects has not been tested. Seven men completed three five-day conditions operationally defined as LEA (15 kcal kg fat-free mass (FFM)-1 day-1) with low protein (LEA-LP; 0.8 g protein·kg body weight (BW)-1), LEA with high protein (LEA-HP; 1.7 g protein·kg BW-1) and control (CON; 40 kcal·kg FFM-1·day-1, 1.7 g protein·kg BW-1). In all conditions, participants expended 15 kcal·kg FFM-1·day-1 during supervised cycling sessions. Serum samples were analyzed for markers of bone turnover, IGF-1 and leptin. The decrease in leptin during LEA-LP (-65.6 ± 4.3%) and LEA-HP (-54.3 ± 16.7%) was greater than during CON (-25.4 ± 11.4%; p = 0.02). Decreases in P1NP (p = 0.04) and increases in CTX-I (p = 0.04) were greater in LEA than in CON, suggesting that LEA shifted bone turnover in favour of bone resorption. No differences were found between LEA-LP and LEA-HP. Thus, five days of LEA disrupted bone turnover, but these changes were not attenuated by a high-protein diet.


Assuntos
Reabsorção Óssea/etiologia , Dieta Rica em Proteínas , Proteínas na Dieta/administração & dosagem , Ingestão de Energia/fisiologia , Osteogênese/fisiologia , Projetos Piloto , Adulto , Biomarcadores/sangue , Composição Corporal , Remodelação Óssea/fisiologia , Reabsorção Óssea/sangue , Reabsorção Óssea/fisiopatologia , Metabolismo Energético/fisiologia , Exercício Físico/fisiologia , Humanos , Fator de Crescimento Insulin-Like I/análise , Leptina/sangue , Masculino , Método Simples-Cego
5.
Med Sci Monit ; 27: e929684, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33690263

RESUMO

The treatment measures of medication-related osteonecrosis of the jaw (MRONJ) is a worldwide challenge in oral and maxillofacial surgery because of its unclear pathogenesis. Previous studies suggested that mesenchymal stem cells played important roles in promoting MRONJ lesion healing, but the detailed mechanisms were unknown. Increasing numbers of studies have demonstrated that exosomes derived from mesenchymal stem cells, especially adipose-derived stem cells, have key roles in stem cell-based therapies by accelerating bone remodeling, facilitating angiogenesis, and promoting wound healing. We hypothesized that exosomes derived from adipose-derived stem cells can prevent MRONJ by accelerating gingival healing and enhancing bone remodeling processes. Our results may provide a promising therapeutic option for MRONJ clinical therapy.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/metabolismo , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/prevenção & controle , Exossomos/transplante , Adipócitos/patologia , Tecido Adiposo/patologia , Remodelação Óssea/fisiologia , Exossomos/metabolismo , Exossomos/patologia , Gengiva/patologia , Humanos , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/patologia , Cicatrização/fisiologia
6.
Methods Mol Biol ; 2230: 303-323, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33197021

RESUMO

Recent advances have revived interest in the concept of osteocyte perilacunar/canalicular remodeling (PLR) and have motivated efforts to identify the mechanisms regulating this process in bone in the context of normal physiology and pathological conditions. Here, we describe several methods that are evaluating morphological changes associated with PLR function of osteocytes.


Assuntos
Matriz Óssea/ultraestrutura , Remodelação Óssea/fisiologia , Técnicas de Cultura de Células/métodos , Osteócitos/ultraestrutura , Animais , Humanos
7.
Int J Biol Macromol ; 170: 326-335, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33373635

RESUMO

Bone remodeling is a complex event that maintains bone homeostasis. The epigenetic mechanism of the regulation of bone remodeling has been a major research focus over the past decades. Histone acetylation is an influential post-translational modification in chromatin architecture. Acetylation affects chromatin structure by offering binding signals for reader proteins that harbor acetyl-lysine recognition domains. This review summarizes recent data of histone acetylation in bone remodeling. The crux of this review is the functional role of histone acetyltransferases, the key promoters of histone acetylation. The functional regulation of acetylation via noncoding RNAs in bone remodeling is also discussed. Understanding the principles governing histone acetylation in bone remodeling would lead to the development of better epigenetic therapies for bone diseases.


Assuntos
Remodelação Óssea/genética , Remodelação Óssea/fisiologia , Histona Acetiltransferases/metabolismo , Acetilação , Animais , Cromatina/genética , Epigênese Genética/genética , Histona Acetiltransferases/genética , Histona Acetiltransferases/fisiologia , Histonas/metabolismo , Humanos , Lisina/química , Regiões Promotoras Genéticas/genética , Processamento de Proteína Pós-Traducional/genética , Transferases/metabolismo
8.
Front Endocrinol (Lausanne) ; 11: 531926, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33362710

RESUMO

Background: In adults, excess adiposity has been associated with low-grade, chronic inflammation and compromised bone health, but less is known about these linkages in children. The purpose of this study was to compare the circulating levels of inflammatory cytokines, adipokines, osteokines, and bone markers at rest and in response to plyometric exercise between obese and normal weight adolescent females. Methods: Ten normal weight (BMI = 21.3 ± 2) and 10 obese (BMI = 32.9 ± 4), postmenarcheal females, aged 13-17 years, performed one bout of plyometric exercise (5 circuits; 120 jumps). Blood samples were taken at rest, 5 min, 1 h, and 24 h post-exercise. Tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), insulin, leptin, osteocalcin, carboxy-terminal telopeptide (CTX), sclerostin, and parathyroid hormone (PTH) were measured in serum. Results: Cytokines were not different between groups at rest or over time with IL-6 increasing (+31%; p = 0.04) 5 min post-exercise and TNF-α decreasing (-9%; p = 0.001) 1 h post-exercise. Insulin and leptin were higher in the obese compared to the normal weight females. In both groups, insulin significantly increased 5 min post-exercise but remained elevated 1 h post-exercise only in the obese group. Leptin did not change in response to exercise. Osteocalcin was lower in the obese group across time and increased (+12%; p = 0.02) 24 h post-exercise in both groups. CTX was similar between groups at rest and decreased (-24%; p < 0.001) 1 h post-exercise. Sclerostin was similar between groups at rest, but there was a significant interaction reflecting a significant increase (+29%; p = 0.04) 5 min post-exercise in the obese group and a non-significant decrease (-13%; p = 0.08) in normal weight controls. PTH increased 5 min post-exercise, dropped 1 h post-exercise to lower than pre-exercise, and returned to baseline 24 h post-exercise in both groups. Conclusion: Obese adolescent females from our study had no evidence of resting inflammation or differences in bone resorption but show blunted bone formation when compared to normal weight controls. The direction and temporal changes in inflammatory cytokines, adipokines, and bone turnover markers to exercise were similar in both groups, reflecting an overall bone anabolic response for most biomarkers, except sclerostin, which increased only in the obese females immediately post-exercise, suggesting a different systemic regulation of sclerostin depending on adiposity.


Assuntos
Adipocinas/sangue , Citocinas/sangue , Exercício Físico/fisiologia , Osteocalcina/sangue , Hormônio Paratireóideo/sangue , Obesidade Pediátrica/sangue , Adolescente , Biomarcadores/sangue , Remodelação Óssea/fisiologia , Feminino , Humanos
9.
Curr Opin Endocrinol Diabetes Obes ; 27(4): 248-252, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32618637

RESUMO

PURPOSE OF REVIEW: An increase in awareness of vegetarian and vegan (plant-based) diets has brought forth numerous studies on their effects on health. The study of nutrition-based factors affecting bone health is difficult, given the length of time before clinical effects are evident. Furthermore, population-based studies must account for strong confounding influences as effects may be because of association, not causality. Yet, it is highly plausible that dietary factors affect bone remodeling in multiple ways. Plant-based diets may alter macronutrient and micronutrient balance, may cause differences in prebiotic and probiotic effects on gut microbiota, and may subtly change the inflammatory and immune response. RECENT FINDINGS: Several recent studies have looked at plant-based nutrition and markers of bone health, using measures such as bone turnover markers, bone mineral density, or fracture rates. Although population based and cross-sectional studies can be prone to confounding effects, a majority did not show differences in bone health between vegetarians/vegans and omnivores as long as calcium and vitamin D intake were adequate. A few prospective cohort or longitudinal studies even demonstrate some benefit to a plant-based diet, but this claim remains unproven. SUMMARY: There is no evidence that a plant-based diet, when carefully chosen to maintain adequate calcium and vitamin D levels, has any detrimental effects on bone health. Theoretical findings suggest a long-term plant-based diet may reduce the risk of osteoporosis, through mechanisms that are currently speculative.


Assuntos
Densidade Óssea/fisiologia , Osso e Ossos/fisiologia , Dieta Vegana , Dieta Vegetariana , Remodelação Óssea/fisiologia , Cálcio/sangue , Dieta Vegana/efeitos adversos , Dieta Vegana/estatística & dados numéricos , Dieta Vegetariana/efeitos adversos , Dieta Vegetariana/estatística & dados numéricos , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/prevenção & controle , Humanos , Estado Nutricional/fisiologia , Osteoporose/epidemiologia , Osteoporose/etiologia , Osteoporose/prevenção & controle , Fatores de Risco , Vitamina D/sangue
10.
Int J Occup Environ Med ; 11(3): 140-147, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32683426

RESUMO

BACKGROUND: The major portion of lead in the body resides in skeletal system. The bone turnover affects the release of lead into the circulation from bones. The bone turnover biomarkers (BTM) in lead-battery workers with long-term exposure to lead have not been explored yet. OBJECTIVE: To evaluate the BTM (formation and resorption) in lead-battery workers with long-term exposure to lead in lead-battery manufacturing plant. METHODS: 176 male lead-exposed workers and 80 matched comparison group were studied. All participants were examined for blood lead levels (BLLs), bone formation biomarkers- serum osteocalcin (OC), alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP)-and bone resorption biomarkers-serum pyridinoline (PYD), deoxypyridinoline (DPYD), tartarate-resistant acid phosphatase-5b (TRACP-5b), and urinary hydroxyproline (UHYP). RESULTS: We found a significantly higher bone formation biomarkers such as BALP (p=0.007) and bone resorption biomarkers, eg, PYD (p=0.048), TRCAP-5b (p=0.001), and UHYP (p=0.001) in lead-exposed workers. A significant (p=0.041) negative correlation (ρ ­0.128) was noted between BLLs and OC. A significant positive correlation was noted between BLLs and TRACP-5b (ρ 0.176, p=0.005) and UHYP (ρ 0.258, p=0.004). Serum OC (p=0.040) and UHYP (p=0.015) levels changed significantly with BLL level. Bone resorption biomarkers levels- PYD, TRACP-5b, and BALP-were higher among those with higher BLLs levels. The duration of exposure was significantly associated with BALP (p=0.037), DPYD (p=0.016), TRACP-5b (p=0.001), and UHYP (p=0.002) levels. CONCLUSION: Long-term lead exposure affects the bone turnover.


Assuntos
Biomarcadores/sangue , Remodelação Óssea/fisiologia , Fontes de Energia Elétrica , Chumbo/toxicidade , Exposição Ocupacional/análise , Fosfatase Ácida/sangue , Fosfatase Ácida/metabolismo , Adulto , Fosfatase Alcalina/sangue , Biomarcadores/análise , Reabsorção Óssea/sangue , Estudos de Casos e Controles , Estudos Transversais , Fontes de Energia Elétrica/efeitos adversos , Humanos , Isoenzimas/sangue , Isoenzimas/metabolismo , Chumbo/química , Intoxicação por Chumbo/sangue , Intoxicação por Chumbo/diagnóstico , Masculino , Instalações Industriais e de Manufatura , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/estatística & dados numéricos , Osteocalcina/sangue , Local de Trabalho
11.
Comput Methods Biomech Biomed Engin ; 23(13): 959-967, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32538160

RESUMO

Remodelling and adaptation of bone within the pelvis is believed to be influenced by the mechanical strains generated during locomotion. Variation in the cortical bone thickness observed in the prenatal ilium has been linked to the musculoskeletal loading associated with in utero movements; for example the development of a thicker gluteal cortex is a possible response to contractions of the gluteal muscles. This study examines if the strains generated in the prenatal iliac cortex due to musculoskeletal loading in utero are capable of initiating bone remodelling to either maintain homeostasis or form new bone. Computational modelling techniques were used firstly to predict the muscle forces and resultant joint reaction force acting on the pelvis during a range of in utero movements. Finite element analyses were subsequently performed to calculate the von Mises strains induced in the prenatal ilium. The results demonstrated that strains generated in the iliac cortex were above the thresholds suggested to regulate bone remodelling to either maintain homeostasis or form new bone. Further simulations are required to investigate the extent to which the heterogeneous cortex forms in response to these strains (i.e., remodelling) or if developmental bone modelling plays a more pivotal role.


Assuntos
Feto/fisiologia , Análise de Elementos Finitos , Ílio/crescimento & desenvolvimento , Fenômenos Fisiológicos Musculoesqueléticos , Fenômenos Biomecânicos , Remodelação Óssea/fisiologia , Humanos , Ílio/anatomia & histologia , Ílio/diagnóstico por imagem , Modelos Biológicos , Estresse Mecânico , Microtomografia por Raio-X
12.
Life Sci ; 256: 118008, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32593709

RESUMO

AIMS: We investigate the effects of RT on the mechanical function, gene, and protein expression of key factors involved in bone remodeling during aging. MAIN METHODS: Male rats of 3 and 21 months of age were randomly allocated into four groups (8 per group): young sedentary (YS), young trained (YT), old sedentary (OS), and old trained (OT). RT was performed three times per week (12 weeks). Bone tenacity and stiffness were measured by biomechanical tests and mRNA levels of COL1A1, MEPE, SOST, OPG, BMP-2, PPAR-y, MMP-2-9-13, and TIMP-1 were evaluated by quantitative PCR. COL1A1 protein and MMP-2 activity were detected by western blotting and zymography assays. KEY FINDINGS: Aging increased stiffness, while BMP-2, OPG, COL1A1 and MMP-2 mRNA levels reduced (OS vs YS; p ≤ 0.05). RT increased the tenacity of the femur and reduced PPAR-γ regardless of age (YT vs. YS; OT vs. OS; p ≤ 0.05). RT downregulated SOST mRNA levels only in the OT group (vs. OS group, p ≤ 0.05). RT mitigated the age-associated increase in MMP-9 mRNA levels (p ≤ 0.05). In young animals, upregulation in MEPE, MMP-13, TIMP-1 were observed after RT, as well an increase in COL1A1 protein and MMP-2 activity (p ≤ 0.05). SIGNIFICANCE: RT improved bone tenacity independent of aging, which is relevant for mechanical function, while, at protein levels, RT upregulated MMP-2 activity and collagen 1 only in young rats. This study highlights the importance of exercise on bone health and identifies specific molecular changes in response to RT. Our findings provide insights into the mechanisms involved in age-related changes.


Assuntos
Envelhecimento/fisiologia , Remodelação Óssea/fisiologia , Condicionamento Físico Animal/fisiologia , Treinamento de Força/métodos , Fatores Etários , Animais , Remodelação Óssea/genética , Regulação da Expressão Gênica/fisiologia , Masculino , RNA Mensageiro/genética , Distribuição Aleatória , Ratos , Ratos Wistar
14.
Sports Health ; 12(4): 334-340, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32525466

RESUMO

BACKGROUND: Female runners are at increased risk of stress fractures (SFs) compared with men. Literature is lacking with regard to best practice for preventing and treating SFs in women. The purpose of the study was to compare physiological measures and running-related factors between women of various ages and running abilities with and without a history of running-related SFs. HYPOTHESIS: Women with and without SF histories will differ with regard to medical and menstrual history, bone health, body composition, nutrition, and running history. STUDY DESIGN: Prospective cohort study. LEVEL OF EVIDENCE: Level 2. METHODS: A total of 20 female runners with SF histories were matched based on age and running distance with 20 women without SF histories. Data included medical, menstrual, running, injury, and nutritional histories; blood histology related to nutritional, hormonal, and bone-related risk factors; and bone density, fat, and lean tissue using dual energy x-ray absorptiometry. Paired t tests were used to examine differences between women with and without SF histories, and Spearmen correlations were conducted to examine relationships between physiological factors. RESULTS: Women with SF histories had lower hip bone mineral density compared with women without SF histories (P < 0.05). SF history was moderately correlated with menstrual changes during increased training times (r = 0.580; P < 0.0001) but was not correlated with any other physiological factor. There was a moderate correlation within the SF group (r = 0.65; P = 0.004) for bone markers for resorption and formation both increasing, indicating increased bone turnover. CONCLUSION: Female runners with low hip bone mineral density, menstrual changes during peak training, and elevated bone turnover markers may be at increased risk of SF. CLINICAL RELEVANCE: Female runners need routine screening for risks associated with SF occurrence. As bone mineral density and bone turnover markers are not routinely assessed in this population, important risk factors may be missed.


Assuntos
Fraturas de Estresse/fisiopatologia , Corrida/fisiologia , Adulto , Biomarcadores/sangue , Distribuição da Gordura Corporal , Índice de Massa Corporal , Densidade Óssea/fisiologia , Remodelação Óssea/fisiologia , Feminino , Humanos , Menstruação , Pessoa de Meia-Idade , Condicionamento Físico Humano/fisiologia , Projetos Piloto , Estudos Prospectivos , Fatores de Risco , Fenômenos Fisiológicos da Nutrição Esportiva , Adulto Jovem
15.
Life Sci ; 254: 117809, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32428598

RESUMO

Bone remodeling is a complex and constant process, which is maintained by well-regulated communication among various cells. Extracellular vesicles (EVs) are small vesicles, which could provide a protective environment for the transportation of various functional molecules. It has been shown that EVs could dock with distant and/or neighboring target cells, deliver cargoes to these specific cells and alter their fates. MicroRNAs (miRNAs), single-stranded non-coding RNAs with 22-26 nucleotides, could bind to mRNAs and repress the translation or stimulate the degradation of mRNAs. It is reported that EVs could serve as the mail carriers, which could cargo miRNAs to exchange information between different cells and act through a novel way to regulate signaling pathways during bone remodeling. In this review, we summarize the function of EV-miRNAs in the communication among mesenchymal stem cells (MSCs), osteoblasts, osteoclasts, osteocytes, and myoblasts during bone remodeling, as well as the key signaling molecules which are involved in this process. The roles of EV-miRNAs in sending intercellular messages in the microenvironment of bone remodeling could shed new light on the development of tissue engineering, and provide novel diagnostic markers and therapeutic targets of bone-related diseases.


Assuntos
Remodelação Óssea/fisiologia , Comunicação Celular/fisiologia , Vesículas Extracelulares/metabolismo , MicroRNAs/metabolismo , Animais , Humanos , Células-Tronco Mesenquimais/metabolismo , Mioblastos/metabolismo , Osteoblastos/metabolismo , Osteoclastos/metabolismo
16.
Gerontology ; 66(4): 393-400, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32454508

RESUMO

INTRODUCTION: Muscle and bone metabolism are both important for the healing of fractures and the regeneration of injured muscle tissue. The aim of this investigation was to evaluate myostatin and other regulating factors in patients with hip fractures who underwent hemi-arthroplasty. METHODS: Serum levels of myostatin (MSTN), follistatin (FSTN), dickkopf-1 (Dkk1), and periostin (PSTN) as well as markers of bone turnover were evaluated in patients with hip fractures before surgery and twice in the 2 weeks after surgery. These parameters were also evaluated in age- and gender-matched subjects without major musculoskeletal injury. RESULTS: MSTN was transiently reduced; its opponent FSTN was transiently increased. Dkk1, the negative regulator of bone mass, and PSTN, a marker of subperiosteal bone formation, increased after surgery. With regard to markers of bone turnover, resorption was elevated during the entire period of observation whereas the early bone formation marker N-terminal propeptide of type I collagen was elevated 12 days after surgery. CONCLUSIONS: Unexpectedly, MSTN, a negative regulator of muscle growth, was reduced after surgery compared with before surgery. As musculoskeletal markers are altered during bone healing, they do not reflect general bone metabolism after fracture or joint arthroplasty. This is important because many elderly patients receive treatment for osteoporosis.


Assuntos
Artroplastia de Quadril , Hemiartroplastia , Fraturas do Quadril/sangue , Miostatina/sangue , Idoso , Idoso de 80 Anos ou mais , Áustria , Biomarcadores/sangue , Proteínas Morfogenéticas Ósseas/sangue , Remodelação Óssea/fisiologia , Estudos de Casos e Controles , Moléculas de Adesão Celular/sangue , Feminino , Folistatina/sangue , Fraturas do Quadril/cirurgia , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Osteogênese/fisiologia , Estudos Prospectivos
17.
Cell Prolif ; 53(5): e12810, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32472648

RESUMO

OBJECTIVES: Gli1+ cells have received extensive attention in tissue homeostasis and injury mobilization. The aim of this study was to investigate whether Gli1+ cells respond to force and contribute to bone remodelling. MATERIALS AND METHODS: We established orthodontic tooth movement (OTM) model to assess the bone response for mechanical force. The transgenic mice were utilized to label and inhibit Gli1+ cells, respectively. Additionally, mice that conditional ablate Yes-associated protein (Yap) in Gli1+ cells were applied in the present study. The tooth movement and bone remodelling were analysed. RESULTS: We first found Gli1+ cells expressed in periodontal ligament (PDL). They were proliferated and differentiated into osteoblastic cells under tensile force. Next, both pharmacological and genetic Gli1 inhibition models were utilized to confirm that inhibition of Gli1+ cells led to arrest of bone remodelling. Furthermore, immunofluorescence staining identified classical mechanotransduction factor Yap expressed in Gli1+ cells and decreased after suppression of Gli1+ cells. Additionally, conditional ablation of Yap gene in Gli1+ cells inhibited the bone remodelling as well, suggesting Gli1+ cells are force-responsive cells. CONCLUSIONS: Our findings highlighted that Gli1+ cells in PDL directly respond to orthodontic force and further mediate bone remodelling, thus providing novel functional evidence in the mechanism of bone remodelling and first uncovering the mechanical responsive property of Gli1+ cells.


Assuntos
Remodelação Óssea/fisiologia , Osso e Ossos/metabolismo , Osso e Ossos/fisiologia , Proteína GLI1 em Dedos de Zinco/metabolismo , Animais , Diferenciação Celular/fisiologia , Mecanotransdução Celular/fisiologia , Camundongos , Camundongos Transgênicos , Osteoclastos/metabolismo , Osteoclastos/fisiologia , Ligamento Periodontal/metabolismo , Ligamento Periodontal/fisiologia , Estresse Mecânico , Técnicas de Movimentação Dentária/métodos
18.
J Nutr Health Aging ; 24(5): 485-493, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32346686

RESUMO

BACKGROUND: The incidence of osteoporosis (OP) is increasing year by year. researches have shown that there was an intense link between the vitamin D (VitD) status and the efficacy of zoledronate (ZOL) in patients with osteoporosis. Since VitD is related to the geogen, its promotion effect on zoledronate has regional specificity. AIM: Combining dual-energy X-ray and bone turnover markers (BTM) to explore the VitD level in postmenopausal osteoporosis patients in Harbin and monitor its effect on the anti-osteoporosis effect of ZOL. METHODS: A total of 120 patients with postmenopausal osteoporosis (PMO) were enrolled .These patients were divided into two groups with 25(OH)D levels = 10ng/ml as a critical point, and each group was randomly divided into experimental groups and control groups). All of the patients were conducted 5 mg ZOL. Then the experimental group was given calcitriol and calcium carbonate, and the control group was only given calcium carbonate. BTM were measured at baseline, 24h, 3 months and 6 months. We also measured bone mineral density (BMD) of bilateral hips (TH BMD) and lumbar spine (LS BMD) at baseline and 6 months. RESULTS: The VitD deficiency rates of the patients enrolled were 84.1%. There was an inverse relationship between the baseline level of VitD and the serum levels of P1NP / ß-CTX, (r=-0.452,p=0.00; r=-0.225, p=0.01). Comparing with baseline, the level of serum P1NP,ß-CTX in each group declined significantly after the treatment (P<0.05). The mean decreasing rates of P1NP and ß-CTX in the both experimental groups were significantly higher than that of the corresponding control groups at the same time point (P<0.05), after 6 months of medication. Both TH BMD and LS BMD at 6 months increased significantly. The increase rate of LS BMD in the high VitD experimental group was significantly higher than the other three groups (P<0.05), the increase rates of TH BMD in the low VitD control group were significantly lower than the other three groups (P<0.05). CONCLUSIONS: The levels of serum VitD in the patients enrolled in this study were generally low. VitD could increase the therapeutic effect of ZOL on osteoporosis.


Assuntos
Biomarcadores/sangue , Conservadores da Densidade Óssea/uso terapêutico , Densidade Óssea/fisiologia , Remodelação Óssea/fisiologia , Osteoporose Pós-Menopausa/tratamento farmacológico , Vitamina D/uso terapêutico , China , Feminino , Humanos , Pessoa de Meia-Idade , Vitamina D/sangue
19.
Niger J Clin Pract ; 23(4): 568-573, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32246667

RESUMO

Objectives: The applied orthodontic force causes remodeling of the periodontium through the selective release of cytokines causing resorption of bone, enabling controlled movement of the tooth. This study compared the cytokine profile between patients treated with conventional labial and lingual fixed orthodontic appliances. Patients and Methods: The study included 80 patients in need of orthodontic treatment, out of which 40 patients were treated by the labial fixed appliance and 40 by the lingual fixed appliance. Gingival crevicular fluid (GCF) specimens were gathered from both the groups using a microcapillary pipette. The samples were collected at the beginning of the treatment and after 21 days. Enzyme-linked immunosorbent assay was performed to evaluate the cytokine levels. Results: Interleukin (IL)-1α, 1ß, 2, 8, and tumor necrosis factor-alpha (TNF-α) levels were significantly high (P < 0.001) in GCF of participants treated with conventional labial fixed appliance. IL-1α, 1ß, 2, 6, 8, and TNF-α levels were significantly high (P < 0.001) in GCF of participants treated by the lingual fixed appliance. The concentrations of TNF-α and IL-1ß were increased higher than other cytokines in both the treatment groups. Conclusion: Overall, the lingual fixed appliance had higher cytokine levels than a labial fixed appliance. Analyzing the GCF cytokine levels during orthodontic treatment could provide an ideal platform for monitoring the progress of the treatment.


Assuntos
Remodelação Óssea/fisiologia , Osso e Ossos/metabolismo , Citocinas/análise , Aparelhos Ortodônticos Fixos/estatística & dados numéricos , Biomarcadores/análise , Líquido do Sulco Gengival/química , Humanos
20.
J Vis Exp ; (157)2020 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-32225155

RESUMO

Bone is a connective tissue constituted of osteoblasts, osteocytes, and osteoclasts and a mineralized extracellular matrix, which gives it its strength and flexibility and allows it to fulfill its functions. Bone is continuously exposed to a variety of stimuli, which in pathological conditions can deregulate bone remodeling. To study bone biology and diseases and evaluate potential therapeutic agents, it has been necessary to develop in vitro and in vivo models. This manuscript describes the dissection process and culture conditions of calvarias isolated from neonatal mice to study bone formation and the bone tumor microenvironment. In contrast to in vitro and in vivo models, this ex vivo model allows preservation of the three-dimensional environment of the tissue as well as the cellular diversity of the bone while culturing under defined conditions to simulate the desired microenvironment. Therefore, it is possible to investigate bone remodeling and its mechanisms, as well as the interactions with other cell types, such as the interactions between cancer cells and bone. The assays reported here use calvarias from 5-7 day old BALB/C mice. The hemi-calvarias obtained are cultured in the presence of insulin, breast cancer cells (MDA-MB-231), or conditioned medium from breast cancer cell cultures. After analysis, it was established that insulin induced new bone formation, while cancer cells and their conditioned medium induced bone resorption. The calvarial model has been successfully used in basic and applied research to study bone development and cancer-induced bone diseases. Overall, it is an excellent option for an easy, informative, and low-cost assay.


Assuntos
Remodelação Óssea/fisiologia , Técnicas de Cocultura/métodos , Crânio/fisiologia , Microambiente Tumoral/fisiologia , Animais , Humanos , Camundongos
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