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1.
Osteoarthritis Cartilage ; 26(9): 1225-1235, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29908226

RESUMO

OBJECTIVES: Age-related bone loss is associated with bone marrow adiposity. Adipokines (e.g., visfatin, resistin, leptin) are adipocyte-derived factors with immunomodulatory properties and might influence differentiation of bone marrow-derived mesenchymal stem cells (MSC) in osteoarthritis (OA) and osteoporosis (OP). Thus, the presence of adipokines and MMPs in bone marrow and their effects on MSC differentiation were analyzed. METHODS: MSC and ribonucleic acid (RNA) were isolated from femoral heads after hip replacement surgery of OA or osteoporotic femoral neck fracture (FF) patients. Bone structural parameters were evaluated by microcomputed tomography (µCT). MSC were differentiated towards adipocytes or osteoblasts with/without adipokines. Gene expression (adipokines, bone marker genes, MMPs, TIMPs) and cytokine production was evaluated by realtime-polymerase chain reaction (realtime-PCR) and enzyme-linked immunosorbent assay (ELISA). Matrix mineralization was quantified using Alizarin red S staining. RESULTS: µCT showed an osteoporotic phenotype of FF compared to OA bone (reduced trabecular thickness and increased ratio of bone surface vs volume of solid bone). Visfatin and leptin were increased in FF vs OA. Visfatin induced the secretion of IL-6, IL-8, and MCP-1 during osteogenic and adipogenic differentiation. In contrast to resistin and leptin, visfatin increased MMP2 and MMP13 during adipogenesis. In osteogenically differentiated cells, MMPs and TIMPs were reduced by visfatin. Visfatin significantly increased matrix mineralization during osteogenesis, whereas collagen type I expression was reduced. CONCLUSION: Visfatin-mediated increase of matrix mineralization and reduced collagen type I expression could contribute to bone fragility. Visfatin is involved in impaired bone remodeling at the adipose tissue/bone interface through induction of proinflammatory factors and dysregulated MMP/TIMP balance during MSC differentiation.


Assuntos
Adipogenia/genética , Citocinas/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Nicotinamida Fosforribosiltransferase/metabolismo , Osteogênese/genética , Osteoporose/genética , Adipogenia/efeitos dos fármacos , Densidade Óssea , Diferenciação Celular/genética , Células Cultivadas , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Fraturas do Fêmur/patologia , Regulação da Expressão Gênica , Humanos , Masculino , Células-Tronco Mesenquimais/citologia , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteoporose/fisiopatologia , Fraturas por Osteoporose/patologia , Reação em Cadeia da Polimerase em Tempo Real/métodos
2.
Z Rheumatol ; 75(5): 444-50, 2016 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-27250491

RESUMO

Microscopic fractures (so-called microcracks) or traumatic macrofractures require bone, as the basic scaffold of the human body, to have a high regenerative capability. In order to be able to provide this regenerative capability, bone is in a constant process of remodeling. This finely tuned homeostasis of bone formation and degradation can become disrupted, which leads to osteoporosis or other bone disorders. It has been shown that the immune system is substantially involved in the regulation of bone homeostasis and that chronic inflammation in particular can disturb this balance; therefore, this article reviews the osteoimmunological aspects contributing to osteoporosis and other diseases associated with bone degradation.


Assuntos
Osso e Ossos/imunologia , Citocinas/imunologia , Imunidade Inata/imunologia , Osteíte/imunologia , Osteoporose/imunologia , Doenças Reumáticas/imunologia , Humanos , Modelos Imunológicos , Osteíte/etiologia , Osteogênese/imunologia , Osteoporose/complicações , Doenças Reumáticas/etiologia
4.
Z Rheumatol ; 73(4): 342-8, 2014 May.
Artigo em Alemão | MEDLINE | ID: mdl-24811358

RESUMO

A finely balanced relationship between bone resorption and bone formation is characteristic for a healthy bone metabolism. Osteoblasts are responsible for bone formation and osteoclasts for bone resorption. In general inflammatory and in particular chronic inflammatory processes influence osteoblast and osteoclast function directly or via indirect mechanisms. Bone metabolism can be influenced by the interaction of cytokines, hormones and growth factors with bone cells. A central factor involved in bone metabolism is the receptor activator of nuclear factor-κB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system, which is influenced by different inflammatory processes. Usually, (chronic) inflammation results in increased bone loss. The molecular mechanisms and pathophysiological pathways of bone metabolism under the influence of inflammation are summarized in this review.


Assuntos
Densidade Óssea/fisiologia , Osso e Ossos/metabolismo , Inflamação/fisiopatologia , Reabsorção Óssea/fisiopatologia , Humanos , Osteoblastos/fisiologia , Osteoclastos/fisiologia , Osteogênese/fisiologia , Osteoprotegerina/fisiologia , Ligante RANK/fisiologia , Receptor Ativador de Fator Nuclear kappa-B/fisiologia
5.
Z Rheumatol ; 71(6): 460-7, 2012 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-22875571

RESUMO

Even though biologics, frequently combined with conventional DMARD therapy, represent a significant advance in the treatment of rheumatic diseases, they have disadvantages such as high costs of production and parenteral administration. Therefore, oral small-molecule drugs are a potential alternative. Major targets for such small-molecule therapeutics are intracellular signaling molecules. This article will briefly discuss potential intracellular targets for therapeutics in the field of rheumatic diseases. How therapeutic signaling inhibitors will be used in clinical practice will depend on a number of factors: their overall effectiveness, their effectiveness in patients who did not or insufficiently respond to conventional DMARD therapy and/or treatment with biologics, their effectiveness when combined with other therapeutics, their side effects, and their cost-benefit ratio.The English full-text version of this article is available at SpringerLink (under "Supplemental").


Assuntos
Antirreumáticos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Espaço Intracelular/metabolismo , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Humanos , Espaço Intracelular/efeitos dos fármacos
7.
Rheumatology (Oxford) ; 47 Suppl 5: v27-8, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18784135

RESUMO

Endothelin (ET) receptors are widely expressed within the human body with one of their major functions being regulation of the vascular tone. Pulmonary arterial hypertension and other complications associated with SSc are related to the function and or dysregulation of these receptors. As ET receptors also play a crucial role in SSc, this review will discuss the expression and physiological functions of ET receptors in the human organism, their signalling pathways, the complications of diseases they are associated with and their importance as a therapeutic target in SSc.


Assuntos
Receptor de Endotelina A/metabolismo , Receptor de Endotelina B/metabolismo , Escleroderma Sistêmico/metabolismo , Transdução de Sinais/fisiologia , Vasos Coronários/metabolismo , Antagonistas do Receptor de Endotelina A , Antagonistas do Receptor de Endotelina B , Humanos , Córtex Renal/metabolismo , Músculo Liso Vascular/metabolismo , Receptor de Endotelina A/análise , Receptor de Endotelina B/análise , Escleroderma Sistêmico/tratamento farmacológico , Vasoconstrição/fisiologia
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