Total hip-and total knee arthroplasties (THA/TKA) are effective treatments for end-stage hip/knee osteoarthritis, leading to satisfactory improvement of pain/function in 80-90% of the patients... Show moreTotal hip-and total knee arthroplasties (THA/TKA) are effective treatments for end-stage hip/knee osteoarthritis, leading to satisfactory improvement of pain/function in 80-90% of the patients within 12-months after surgery. Overall, knowledge regarding clinical outcomes reflecting the process of recovery in patients undergoing THA/TKA over a prolonged period is scarce. First, this thesis addressed the successfull feasibility of collecting a comprehensive set of outcomes relevant for the process of recovery. Second, it was found that the decrease in pain/improvement in function after 1 -year in THA-patients, but not in TKA-patients, was positively associated with more preoperative radiographic severity of OA. Thirdly, most patients’ preoperative expectations of outcomes of THA/TKA regarding functioning were met, unfortunately more frequently not in TKA-patients. Finally, 90%/52% of THA/TKA-patients return after surgery after 12-weeks on average. However, despite high return-to-work rates, a considerable proportion of the patients who return-to-work, worked less hours than preoperatively. Concluding, although overall favourable outcomes were seen, this thesis identified a number of areas for improvement: better identification of subgroups with a likely perceived unsuccessful outcome or recovery process, if not preoperatively then early after surgery. Early identification and subsequent interventions may change the course of recovery of THA/TKA for such patients, leading to added value in this subgroup. Show less
In dit proefschrift worden de moleculaire mechanismen behandeld die onderliggend zijn aan artrose. Specifiek wordt genoomwijd onderzocht welke genen anders tot expressie komen in aangedaan... Show moreIn dit proefschrift worden de moleculaire mechanismen behandeld die onderliggend zijn aan artrose. Specifiek wordt genoomwijd onderzocht welke genen anders tot expressie komen in aangedaan vergeleken met gezond kraakbeen van artrose patienten. Dit in de context van epigenetische regulatie van gen expressie, specifiek door DNA methylatie in het licht van de lokale genetische context in de vorm van puntmutaties. Show less
Immunometabolism focusses on the interplay between immunological and metabolic processes, both at a systemic and a cellular level. This thesis is divided into two parts based on these two... Show moreImmunometabolism focusses on the interplay between immunological and metabolic processes, both at a systemic and a cellular level. This thesis is divided into two parts based on these two levels. The first part focusses on the infrapatellar fat pad (IFP), an adipose tissue located in the knee, and the potential role in the pathophysiology of osteoarthritis. Therefore, we characterized the IFP based on a cellular and molecular level and found that the inflammatory state of the joint does affect the cellular load of the IFP, however, the secretory profile of the IFP does not seem to be affected. Furthermore, obesity-related changes normally found in adipose tissue were not present in the IFP. When characterizing the IFP we found two interesting cell populations, IL-6-secreting T cells and macrophages with an anti-inflammatory phenotype secreting pro-inflammatory cytokines. Both populations could be involved in the pathophysiology of the osteoarthritic joint. Furthermore, in the second part we focussed on cellular metabolism where we determined the mechanism by which fatty acids exert their effect on T cells. We found that fatty acids are not served as energy, however, whether it is used for daughter cells or influencing cell signalling remains to be elucidated. Show less
Kloppenburg, M.; Beest, S. van; Kroon, F.P.B. 2017
In the field of Osteoarthritis (OA) research the step from genetics to biological functionality, also named ‘functional genomics’, is necessary to allow valorisation of genetic findings, thereby... Show moreIn the field of Osteoarthritis (OA) research the step from genetics to biological functionality, also named ‘functional genomics’, is necessary to allow valorisation of genetic findings, thereby augmenting the need for functional data of disease relevant tissues. Even so, it was estimated that pursuing druggable targets directed by genetic studies are twice as often successful as compared to those without it. In this thesis we apply the functional genomics methodology, to proceed from a genetic association to mechanistic understanding of the effect of genetic variation on gene expression and epigenetic regulation contributing to OA susceptibility. Particularly we set out to characterize and validate the pathophysiological processes that underlie the role of DIO2/thyroid hormone signalling in the onset of OA after identifying the DIO2 gene as a OA susceptibility locus. The results in this thesis show that intracellular T3 levels should be strictly regulated via DIO2 upon mechanical loading of the cartilage, to ensure cartilage tissue homeostasis. Future endeavours should be designed to demonstrate that local inhibition of DIO2 by intra-articular admission of a deiodinase-inhibitor (Iopanoic acid), could be an effective therapy to alleviate the burden of OA thereby increasing mobility, well-being and quality of life particularly among elderly. Show less
Swart, N.M.; Oudenaarde, K. van; Reijnierse, M.; Nelissen, R.G.H.H.; Verhaar, J.A.N.; Bierma-Zeinstra, S.M.A.; Luijsterburg, P.A.J. 2016
Conclusion: An impaired glucose metabolism does not seem be related to OA. In men, an association was observed for fasting glucose concentrations and hand OA. Future studies should investigate the... Show moreConclusion: An impaired glucose metabolism does not seem be related to OA. In men, an association was observed for fasting glucose concentrations and hand OA. Future studies should investigate the presence of sex differences in the pathogenesis of hand OA. (C) 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. Show less
Conclusions: Assessment of progression in hand OA defined by JSW measurements is possible, but performs less well than progression defined by JSN scoring. Therefore, the value of JSW measurements... Show moreConclusions: Assessment of progression in hand OA defined by JSW measurements is possible, but performs less well than progression defined by JSN scoring. Therefore, the value of JSW measurements in hand OA clinical trials remains questionable. (C) 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. Show less
