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1.
Cartilage ; 14(1): 67-75, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36546648

RESUMO

OBJECTIVES: Previously, we have shown the involvement of cellular communication network factor 4/Wnt-activated protein Wnt-1-induced signaling protein 1 (CCN4/WISP1) in osteoarthritic (OA) cartilage and its detrimental effects on cartilage. Here, we investigated characteristics of CCN4 in chondrocyte biology by exploring correlations of CCN4 with genes expressed in human OA cartilage with functional follow-up. DESIGN: Spearman correlation analysis was performed for genes correlating with CCN4 using our previously established RNA sequencing dataset of human preserved OA cartilage of the RAAK study, followed by a pathway enrichment analysis for genes with ρ ≥|0.6.| Chondrocyte migration in the absence or presence of CCN4 was determined in a scratch assay, measuring scratch size using a live cell imager for up to 36 h. Changes in expression levels of 12 genes, correlating with CCN4 and involved in migratory processes, were determined with reverse transcription-quantitative polymerase chain reaction (RT-qPCR). RESULTS: Correlation of CCN4 with ρ ≥|0.6| was found for 58 genes in preserved human OA cartilage. Pathway analysis revealed "neural crest cell migration" as most significant enriched pathway, containing among others CORO1C, SEMA3C, and SMO. Addition of CCN4 to primary chondrocytes significantly enhance chondrocyte migration as demonstrated by reduced scratch size over the course of 36 h, but at the timepoints measured no effect was observed on mRNA expression of the 12 genes. CONCLUSION: CCN4 increases cell migration of human primary OA chondrocytes. Since WISP1 expression is known to be increased in OA cartilage, this may serve to direct chondrocytes toward cartilage defects and orchestrate repair.


Assuntos
Cartilagem Articular , Condrócitos , Humanos , Condrócitos/metabolismo , Cartilagem Articular/metabolismo , Células Cultivadas , Diferenciação Celular , Transdução de Sinais
2.
Arthritis Rheumatol ; 73(5): 789-799, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33258547

RESUMO

OBJECTIVE: To identify key determinants of the interactive pathophysiologic processes in subchondral bone and cartilage in osteoarthritis (OA). METHODS: We performed RNA sequencing on macroscopically preserved and lesional OA subchondral bone from patients in the Research Arthritis and Articular Cartilage study who underwent joint replacement surgery due to OA (n = 24 sample pairs: 6 hips and 18 knees). Unsupervised hierarchical clustering and differential expression analyses were conducted. Results were combined with data on previously identified differentially expressed genes in cartilage (partly overlapping samples) as well as data on recently identified OA risk genes. RESULTS: We identified 1,569 genes that were significantly differentially expressed between lesional and preserved subchondral bone, including CNTNAP2 (fold change [FC] 2.4, false discovery rate [FDR] 3.36 × 10-5 ) and STMN2 (FC 9.6, FDR 2.36 × 10-3 ). Among these 1,569 genes, 305 were also differentially expressed, and with the same direction of effect, in cartilage, including the recently recognized OA susceptibility genes IL11 and CHADL. Upon differential expression analysis with stratification for joint site, we identified 509 genes that were exclusively differentially expressed in subchondral bone of the knee, including KLF11 and WNT4. These genes that were differentially expressed exclusively in the knee were enriched for involvement in epigenetic processes, characterized by, e.g., HIST1H3J and HIST1H3H. CONCLUSION: IL11 and CHADL were among the most consistently differentially expressed genes OA pathophysiology-related genes in both bone and cartilage. As these genes were recently also identified as robust OA risk genes, they classify as attractive therapeutic targets acting on 2 OA-relevant tissues.


Assuntos
Osso e Ossos/metabolismo , Cartilagem Articular/metabolismo , Proteínas da Matriz Extracelular/genética , Interleucina-11/genética , Osteoartrite do Quadril/genética , Osteoartrite do Joelho/genética , Idoso , Idoso de 80 Anos ou mais , Proteínas Reguladoras de Apoptose/genética , Análise por Conglomerados , Feminino , Humanos , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Osteoartrite do Quadril/cirurgia , Osteoartrite do Joelho/cirurgia , RNA Mensageiro/metabolismo , RNA-Seq , Proteínas Repressoras/genética , Estatmina/genética , Proteína Wnt4/genética
3.
J Rehabil Med ; 47(3): 278-81, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25521463

RESUMO

OBJECTIVE: To gather preliminary data on the effectiveness of intensive rehabilitation after hip fracture surgery, as provided in the Transfer Unit (TU) in Leiden, The Netherlands, compared with the effectiveness of rehabilitation in a regular nursing home. Intensive rehabilitation in the TU consists of physical therapy twice daily by dedicated medical staff and aims to shorten hospital stay and duration of rehabilitation, in order to increase the hospital admission capacity and reduce waiting lists for nursing homes. DESIGN: Retrospective cohort study. PATIENTS: A total of 173 hip fracture patients, selected postoperatively for intensive rehabilitation in the TU. Of these, 156 received TU rehabilitation (TU+ group), while 17 were rehabilitated in regular nursing homes for logistic reasons (TU- group). METHODS: Length of hospital stay, rehabilitation duration and survival were compared between TU+ and TU-. RESULTS: Both groups appeared comparable at baseline. TU+ patients had a mean hospital stay of 10.4 vs 12.3 days for TU- patients (p = 0.29), while their rehabilitation duration was 25.2 days shorter: 42.0 vs 67.2 days (p = 0.001). One-year survival was similar (87%). CONCLUSION: Intensive rehabilitation in selected hip fracture patients may reduce rehabilitation duration by almost 4 weeks. Differentiated aftercare appears to increase care efficiency for hip fracture patients in both hospitals and nursing homes and may result in a significant reduction in costs.


Assuntos
Fraturas do Quadril/reabilitação , Assistência ao Convalescente/métodos , Assistência ao Convalescente/normas , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Países Baixos , Seleção de Pacientes , Modalidades de Fisioterapia , Estudos Prospectivos , Centros de Reabilitação/organização & administração , Estudos Retrospectivos
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