@article{SadowskaTouliHitzletal.2017, author = {Sadowska, Aleksandra and Touli, Ermioni and Hitzl, Wolfgang and Greutert, Helen and Ferguson, Stephen J. and W{\"u}rtz-Kozak, Karin and Hausmann, Oliver N.}, title = {Inflammaging in cervical and lumbar degenerated intervertebral discs}, series = {European Spine Journal}, volume = {27}, journal = {European Spine Journal}, number = {3}, publisher = {Springer}, address = {New York}, issn = {0940-6719}, doi = {10.1007/s00586-017-5360-8}, pages = {564 -- 577}, year = {2017}, abstract = {To investigate and compare the occurrence of inflammatory processes in the sites of disc degeneration in the lumbar and cervical spine by a gene array and subsequent qPCR and to investigate the mechanistic involvement of transient receptor potential channels TRPC6 and TRPV4. The gene expression of inflammatory cytokines and TRP channels was measured in human disc samples obtained from patients undergoing discectomy at the cervical (n = 24) or lumbar (n = 27) spine for degenerative disc disease (DDD) and disc herniation (DH) and analyzed for differences with regard to spinal level, IVD degeneration grade, Modic grade, age, sex, disc region and surgical extent. Aside from genes with known implication in DDD and DH, four previously unreported genes from the interferon and TRP families (IFNA1, IFNA8, IFNB1, TRPC6) could be detected. A correlation between gene expression and age (IL-15) and IVD degeneration grade (IFNA1, IL-6, IL-15, TRPC6), but not Modic grade, was identified. Significant differences were detected between cervical and lumbar discs (IL-15), nucleus and annulus (IL-6, TNF-alpha, TRPC6), single-level and multi-level surgery (IL-6, IL-8) as well as DDD and DH (IL-8), while sex had no effect. Multiple gene-gene pair correlations, either between different cytokines or between cytokines and TRP channels, exist in the disc. This study supports the relevance of IL-6 and IL-8 in disc diseases, but furthermore points toward a possible pathological role of IL-15 and type I interferons, as well as a mechanistic role of TRPC6. With limited differences in the inflammatory profile of cervical and lumbar discs, novel anti-inflammatory or TRP-modulatory strategies for the treatment of disc pathologies may be applicable independent of the spinal region.}, language = {en} } @article{KrupkovaZvickWuertzKozak2017, author = {Krupkova, Olga and Zvick, Johannes and W{\"u}rtz-Kozak, Karin}, title = {The role of transient receptor potential channels in joint diseases}, series = {European cells \& materials}, volume = {34}, journal = {European cells \& materials}, publisher = {Univ. of Wales}, address = {Aberystwyth}, issn = {1473-2262}, doi = {10.22203/eCM.v034a12}, pages = {180 -- 201}, year = {2017}, abstract = {Transient receptor potential channels (TRP channels) are cation selective transmembrane receptors with diverse structures, activation mechanisms and physiological functions. TRP channels act as cellular sensors for a plethora of stimuli, including temperature, membrane voltage, oxidative stress, mechanical stimuli, pH and endogenous as well as exogenous ligands, thereby illustrating their versatility. As such, TRP channels regulate various functions in both excitable and non-excitable cells, mainly by mediating Ca2+ homeostasis. Dysregulation of TRP channels is implicated in many pathologies, including cardiovascular diseases, muscular dystrophies and hyperalgesia. However, the importance of TRP channel expression, physiological function and regulation in chondrocytes and intervertebral disc (IVD) cells is largely unexplored. Osteoarthritis (OA) and degenerative disc disease (DDD) are chronic age-related disorders that significantly affect the quality of life by causing pain, activity limitation and disability. Furthermore, currently available therapies cannot effectively slow-down or stop progression of these diseases. Both OA and DDD are characterised by reduced tissue cellularity, enhanced inflammatory responses and molecular, structural and mechanical alterations of the extracellular matrix, hence affecting load distribution and reducing joint flexibility. However, knowledge on how chondrocytes and IVD cells sense their microenvironment and respond to its changes is still limited. In this review, we introduced six families of mammalian TRP channels, their mechanisms of activation as well as activation-driven cellular consequences. We summarised the current knowledge on TRP channel expression and activity in chondrocytes and IVD cells and the significance of TRP channels as therapeutic targets for the treatment of OA and DDD.}, language = {en} } @article{FrancoObregonCambriaGreutertetal.2018, author = {Franco-Obregon, Alfredo and Cambria, Elena and Greutert, Helen and Wernas, Timon and Hitzl, Wolfgang and Egli, Marcel and Sekiguchi, Miho and Boos, Norbert and Hausmann, Oliver and Ferguson, Stephen J. and Kobayashi, Hiroshi and W{\"u}rtz-Kozak, Karin}, title = {TRPC6 in simulated microgravity of intervertebral disc cells}, series = {European Spine Journal}, volume = {27}, journal = {European Spine Journal}, number = {10}, publisher = {Springer}, address = {New York}, issn = {0940-6719}, doi = {10.1007/s00586-018-5688-8}, pages = {2621 -- 2630}, year = {2018}, abstract = {Purpose Prolonged bed rest and microgravity in space cause intervertebral disc (IVD) degeneration. However, the underlying molecular mechanisms are not completely understood. Transient receptor potential canonical (TRPC) channels are implicated in mechanosensing of several tissues, but are poorly explored in IVDs. Methods Primary human IVD cells from surgical biopsies composed of both annulus fibrosus and nucleus pulposus (passage 1-2) were exposed to simulated microgravity and to the TRPC channel inhibitor SKF-96365 (SKF) for up to 5days. Proliferative capacity, cell cycle distribution, senescence and TRPC channel expression were analyzed. Results Both simulated microgravity and TRPC channel antagonism reduced the proliferative capacity of IVD cells and induced senescence. While significant changes in cell cycle distributions (reduction in G1 and accumulation in G2/M) were observed upon SKF treatment, the effect was small upon 3days of simulated microgravity. Finally, downregulation of TRPC6 was shown under simulated microgravity. Conclusions Simulated microgravity and TRPC channel inhibition both led to reduced proliferation and increased senescence. Furthermore, simulated microgravity reduced TRPC6 expression. IVD cell senescence and mechanotransduction may hence potentially be regulated by TRPC6 expression. This study thus reveals promising targets for future studies.}, language = {en} } @misc{KrupkovaSmoldersWuertzKozaketal.2018, author = {Krupkova, Olga and Smolders, Lucas and W{\"u}rtz-Kozak, Karin and Cook, James and Pozzi, Antonio}, title = {The pathobiology of the meniscus}, series = {Frontiers in veterinary science}, volume = {5}, journal = {Frontiers in veterinary science}, publisher = {Frontiers Research Foundation}, address = {Lausanne}, issn = {2297-1769}, doi = {10.3389/fvets.2018.00073}, pages = {15}, year = {2018}, abstract = {Serious knee pain and related disability have an annual prevalence of approximately 25\% on those over the age of 55 years. As curative treatments for the common knee problems are not available to date, knee pathologies typically progress and often lead to osteoarthritis (OA). While the roles that the meniscus plays in knee biomechanics are well characterized, biological mechanisms underlying meniscus pathophysiology and roles in knee pain and OA progression are not fully clear. Experimental treatments for knee disorders that are successful in animal models often produce unsatisfactory results in humans due to species differences or the inability to fully replicate disease progression in experimental animals. The use of animals with spontaneous knee pathologies, such as dogs, can significantly help addressing this issue. As microscopic and macroscopic anatomy of the canine and human menisci are similar, spontaneous meniscal pathologies in canine patients are thought to be highly relevant for translational medicine. However, it is not clear whether the biomolecular mechanisms of pain, degradation of extracellular matrix, and inflammatory responses are species dependent. The aims of this review are (1) to provide an overview of the anatomy, physiology, and pathology of the human and canine meniscus, (2) to compare the known signaling pathways involved in spontaneous meniscus pathology between both species, and (3) to assess the relevance of dogs with spontaneous meniscal pathology as a translational model. Understanding these mechanisms in human and canine meniscus can help to advance diagnostic and therapeutic strategies for painful knee disorders and improve clinical decision making.}, language = {en} } @misc{SadowskaKamedaKrupkovaetal.2018, author = {Sadowska, Aleksandra and Kameda, Takuya and Krupkova, Olga and W{\"u}rtz-Kozak, Karin}, title = {Osmosensing, osmosignalling and inflammation}, series = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, number = {693}, issn = {1866-8364}, doi = {10.25932/publishup-46908}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-469080}, pages = {22}, year = {2018}, abstract = {Intervertebral disc (IVD) cells are naturally exposed to high osmolarity and complex mechanical loading, which drive microenvironmental osmotic changes. Age- and degeneration-induced degradation of the IVD's extracellular matrix causes osmotic imbalance, which, together with an altered function of cellular receptors and signalling pathways, instigates local osmotic stress. Cellular responses to osmotic stress include osmoadaptation and activation of pro-inflammatory pathways. This review summarises the current knowledge on how IVD cells sense local osmotic changes and translate these signals into physiological or pathophysiological responses, with a focus on inflammation. Furthermore, it discusses the expression and function of putative membrane osmosensors (e.g. solute carrier transporters, transient receptor potential channels, aquaporins and acid-sensing ion channels) and osmosignalling mediators [e.g. tonicity responseelement-binding protein/nuclear factor of activated T-cells 5 (TonEBP/NFAT5), nuclear factor kappa-lightchain-enhancer of activated B cells (NF-kappa B)] in healthy and degenerated IVDs. Finally, an overview of the potential therapeutic targets for modifying osmosensing and osmosignalling in degenerated IVDs is provided.}, language = {en} } @article{LoepfeDussZafeiropoulouetal.2019, author = {L{\"o}pfe, Moira and Duss, Anja and Zafeiropoulou, Katerina-Alexandra and Bjoergvinsdottir, Oddny and Eglin, David and Fortunato, Giuseppino and Klasen, J{\"u}rgen and Ferguson, Stephen J. and W{\"u}rtz-Kozak, Karin and Krupkova, Olga}, title = {Electrospray-Based Microencapsulation of Epigallocatechin 3-Gallate for Local Delivery into the Intervertebral Disc}, series = {Pharmaceutics}, volume = {11}, journal = {Pharmaceutics}, number = {9}, publisher = {MDPI}, address = {Basel}, issn = {1999-4923}, doi = {10.3390/pharmaceutics11090435}, pages = {15}, year = {2019}, abstract = {Locally delivered anti-inflammatory compounds can restore the homeostasis of the degenerated intervertebral disc (IVD). With beneficial effects on IVD cells, epigallocatechin 3-gallate (EGCG) is a promising therapeutic candidate. However, EGCG is prone to rapid degradation and/or depletion. Therefore, the purpose of this study was to develop a method for controlled EGCG delivery in the degenerated IVD. Primary IVD cells were isolated from human donors undergoing IVD surgeries. EGCG was encapsulated into microparticles by electrospraying of glutaraldehyde-crosslinked gelatin. The resulting particles were characterized in terms of cytocompatibility and anti-inflammatory activity, and combined with a thermoresponsive carrier to produce an injectable EGCG delivery system. Subsequently, electrospraying was scaled up using the industrial NANOSPIDER (TM) technology. The produced EGCG microparticles reduced the expression of inflammatory (IL-6, IL-8, COX-2) and catabolic (MMP1, MMP3, MMP13) mediators in pro-inflammatory 3D cell cultures. Combining the EGCG microparticles with the carrier showed a trend towards modulating EGCG activity/release. Electrospray upscaling was achieved, leading to particles with homogenous spherical morphologies. In conclusion, electrospray-based encapsulation of EGCG resulted in cytocompatible microparticles that preserved the activity of EGCG and showed the potential to control EGCG release, thus favoring IVD health by downregulating local inflammation. Future studies will focus on further exploring the biological activity of the developed delivery system for potential clinical use.}, language = {en} } @article{PehlivanogluWuertzKozakHeideretal.2019, author = {Pehlivanoglu, Tuna and W{\"u}rtz-Kozak, Karin and Heider, Franziska and Sauer, Daniel and Wanke-Jellinek, Lorenz and Mayer, Michael and Mehren, Christoph}, title = {Clinical and Radiographic Outcome of Patients With Cervical Spondylotic Myelopathy Undergoing Total Disc Replacement}, series = {SPINE}, volume = {44}, journal = {SPINE}, number = {20}, publisher = {Lippincott Williams \& Wilkins}, address = {Philadelphia}, issn = {0362-2436}, doi = {10.1097/BRS.0000000000003079}, pages = {1403 -- 1411}, year = {2019}, abstract = {Study Design. A nonrandomized, prospective, and single-center clinical trial. Objective. The aim of this study was to investigate the clinical and radiographic efficacy of ProDisc Vivo cervical total disc replacement (cTDR) in patients with clinical and radiographic documented cervical spondylotic myelopathy (CSM), due to degenerative changes at the index level. Summary of Background Data. Decompression and fusion is still the gold standard in patients with cervical myelopathy. Very limited data are available regarding the application of cTDR in patients with clinical and radiological documented CSM in context of clinical and radiographic outcomes. Methods. Clinical outcome scores included the Neck Disability Index (NDI), Visual Analogue Scale (VAS), arm and neck pain self-assessment questionnaires as well as the Nurick grade and the Japanese Orthopaedic Association (JOA) score. The radiological outcome included the range of motion (ROM), the segmental and global (C2-C7) lordosis, and the occurrence of heterotopic ossifications. Results. Eighteen consecutive patients (10 males, 8 females) with documented clinical and radiological signs of myelopathy were included in this investigation. The study population had a mean age of 52.4 years and a follow-up period of 20.3 months in average (range 3-48 months). The mean range ROM of the index level stayed consistent with 6.8 degrees preoperatively and 7.2 degrees (P = 0.578) at the last follow-up; the global lordosis in neutral position changed from 3.5 degrees to 14.2 degrees significantly (P = 0.005) in mean. The JOA score improved from 11.3 to 16.6 (P < 0.001) as well as the NDI 36.7 to 10.3 (P < 0.001) and the VAS score from 5.7/6.1 (arm/neck) to 1.3/2.0 (P P < 0.001). The mean Nurick grade was 1.33 preoperatively and dropped down in all cases to Nurick grade of 0 (P < 0.001). Conclusion. cTDR (with ProDisc Vivio) in patients with CSM yielded good clinical and radiographic outcomes and found as a reliable, safe, and motion-preserving surgical treatment option, although its indication is very limited due to numerous exclusion criteria.}, language = {en} } @article{KamedaZvickVuketal.2019, author = {Kameda, Takuya and Zvick, Joel and Vuk, Miriam and Sadowska, Aleksandra and Tam, Wai Kit and Leung, Victor Y. and B{\"o}lcskei, Kata and Helyes, Zsuzsanna and Applegate, Lee Ann and Hausmann, Oliver N. and Klasen, Juergen and Krupkova, Olga and W{\"u}rtz-Kozak, Karin}, title = {Expression and Activity of TRPA1 and TRPV1 in the Intervertebral Disc}, series = {International journal of molecular sciences}, volume = {20}, journal = {International journal of molecular sciences}, number = {7}, publisher = {MDPI}, address = {Basel}, issn = {1422-0067}, doi = {10.3390/ijms20071767}, pages = {23}, year = {2019}, abstract = {Transient receptor potential (TRP) channels have emerged as potential sensors and transducers of inflammatory pain. The aims of this study were to investigate (1) the expression of TRP channels in intervertebral disc (IVD) cells in normal and inflammatory conditions and (2) the function of Transient receptor potential ankyrin 1 (TRPA1) and Transient receptor potential vanilloid 1 (TRPV1) in IVD inflammation and matrix homeostasis. RT-qPCR was used to analyze human fetal, healthy, and degenerated IVD tissues for the gene expression of TRPA1 and TRPV1. The primary IVD cell cultures were stimulated with either interleukin-1 beta (IL-1) or tumor necrosis factor alpha (TNF-) alone or in combination with TRPA1/V1 agonist allyl isothiocyanate (AITC, 3 and 10 mu M), followed by analysis of calcium flux and the expression of inflammation mediators (RT-qPCR/ELISA) and matrix constituents (RT-qPCR). The matrix structure and composition in caudal motion segments from TRPA1 and TRPV1 wild-type (WT) and knock-out (KO) mice was visualized by FAST staining. Gene expression of other TRP channels (A1, C1, C3, C6, V1, V2, V4, V6, M2, M7, M8) was also tested in cytokine-treated cells. TRPA1 was expressed in fetal IVD cells, 20\% of degenerated IVDs, but not in healthy mature IVDs. TRPA1 expression was not detectable in untreated cells and it increased upon cytokine treatment, while TRPV1 was expressed and concomitantly reduced. In inflamed IVD cells, 10 mu M AITC activated calcium flux, induced gene expression of IL-8, and reduced disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) and collagen 1A1, possibly via upregulated TRPA1. TRPA1 KO in mice was associated with signs of degeneration in the nucleus pulposus and the vertebral growth plate, whereas TRPV1 KO did not show profound changes. Cytokine treatment also affected the gene expression of TRPV2 (increase), TRPV4 (increase), and TRPC6 (decrease). TRPA1 might be expressed in developing IVD, downregulated during its maturation, and upregulated again in degenerative disc disease, participating in matrix homeostasis. However, follow-up studies with larger sample sizes are needed to fully elucidate the role of TRPA1 and other TRP channels in degenerative disc disease.}, language = {en} } @article{MouserArkesteijnvanDijketal.2019, author = {Mouser, Vivian H. M. and Arkesteijn, Irene T. M. and van Dijk, Bart G. M. and W{\"u}rtz-Kozak, Karin and Ito, Keita}, title = {Hypotonicity differentially affects inflammatory marker production by nucleus pulposus tissue in simulated disc degeneration versus herniation}, series = {Journal of orthopaedic research}, volume = {37}, journal = {Journal of orthopaedic research}, number = {5}, publisher = {Wiley}, address = {Hoboken}, issn = {0736-0266}, doi = {10.1002/jor.24268}, pages = {1110 -- 1116}, year = {2019}, abstract = {Inflammatory cytokines play an important role in intervertebral disc degeneration. Although largely produced by immune cells, nucleus pulposus (NP) cells can also secrete them under various conditions, for example, under free swelling. Thus, tissue hypotonicity may be an inflammatory trigger for NP cells. The aim of this study was to investigate whether decreased tonicity under restricted swelling conditions (as occurring in early disc degeneration) could initiate an inflammatory cascade that mediates further degeneration. Healthy bovine NP tissue was balanced against different PEG concentrations (0-30\%) to obtain various tissue tonicities. Samples were then placed in an artificial annulus (fixed volume) and were cultured for 3, 7, or 21 days, with free swelling NP as control. Tissue content (water, glycosaminoglycan, collagen) was analyzed, and both the tissue and medium were screened for tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8), prostaglandin-E-2 (PGE(2)), and nitric oxide (NO). A range of tonicities (isotonic to hypotonic) was present at day 3 in the PEG-treated samples. However, during culture, the tonicity range narrowed as GAGs leached from the tissue. TNF-alpha and IL-1 beta were below detection limits in all conditions, while mid- and downstream inflammatory cytokines were detected. This may suggest that the extracellular environment directly affects NP cells instead of inducing a classical inflammatory cascade. Furthermore, IL-8 increased in swelling restricted samples, while IL-6 and PGE(2) were elevated in free swelling controls. These findings may suggest the involvement of different mechanisms in disc degeneration with intact AF compared to herniation, and encourage further investigation. (c) 2019 The Authors. Journal of Orthopaedic Research (R) Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res}, language = {en} } @article{MehrenHeiderSaueretal.2019, author = {Mehren, Christoph and Heider, Franziska and Sauer, Daniel and Kothe, Ralph and Korge, Andreas and Hitzl, Wolfgang and W{\"u}rtz-Kozak, Karin}, title = {Clinical and radiological outcome of a new total cervical disc replacement design}, series = {Spine}, volume = {44}, journal = {Spine}, number = {4}, publisher = {Lippincott Williams \& Wilkins}, address = {Philadelphia}, issn = {0362-2436}, doi = {10.1097/BRS.0000000000002799}, pages = {E202 -- E210}, year = {2019}, abstract = {Study Design. A nonrandomized, prospective, and single- center clinical trial of the ProDisc Vivo prosthesis. Objective. The aim of this study was to investigate the clinical and radiological results of a refined total cervical disc replacement (cTDR), the ProDisc Vivo, with two years of follow-up (FU). The incidence of implant-related complications was recorded as a secondary outcome variable. Summary of Background Data. Previous generations of the ProDisc artificial cervical disc replacement generate high primary stability due to keel-based designs with opening of the anterior cortex during the implantation and subsequent high rates of heterotopic ossifications. Methods. Clinical outcome scores included the Neck Disability Index (NDI), Visual Analogue Scale (VAS), arm and neck pain self-assessment questionnaires. The radiological outcome included the range of motion (ROM) and the occurrence of heterotopic ossifications. The incidence of implant-related complications with new implant design was recorded as a secondary outcome variable. Results. A total of 55 patients received a single-level treatment with the ProDisc Vivo cTDR between C3/4 and C6/7, with a follow-up rate of 78\%. The clinical outcome scores improved in all parameters significantly (P 1/4 0.0001) (NDI: 68.3 -> 17.4; VAS arm: 6.3 -> 1.4; VAS neck: 4.9 -> 1.6). The ROM of the indexsegment did not show a significant change (P 1/4 0.26) (7.9 degrees -> 9.2 degrees). Heterotopic ossifications at the index segment was found as grade 0 in 5\%, grade 1 in 22\%, grade 2 in 10\%, grade 3 (with functional impairment of the prosthesis) in 7\%, and grade 4 in 3\% of the cases. We observed three implant-related complications (5.5\%), with two implant dislocations anteriorly and one low-grade infect. Conclusion. cTDR with ProDisc Vivo demonstrated a significant and sustained improvement of all clinical outcome parameters. A less invasive implantation mechanism with lower primary stability of the cTDR might be a reason for a higher dislocation rate than the keel-based previous generation ProDisc C.}, language = {en} } @misc{WippertBlockMansuyetal.2019, author = {Wippert, Pia-Maria and Block, Andrea and Mansuy, Isabelle M. and Peters, Eva M. J. and Rose, Matthias and Rapp, Michael Armin and Huppertz, Alexander and W{\"u}rtz-Kozak, Karin}, title = {Alterations in Bone Homeostasis and Microstructure Related to Depression and Allostatic Load}, series = {Psychotherapy and Psychosomatics}, volume = {88}, journal = {Psychotherapy and Psychosomatics}, number = {6}, publisher = {Karger}, address = {Basel}, issn = {0033-3190}, doi = {10.1159/000503640}, pages = {383 -- 385}, year = {2019}, language = {en} } @article{HeCazzanelliWuertzKozaketal.2021, author = {He, Yangyang and Cazzanelli, Petra and W{\"u}rtz-Kozak, Karin and Wippert, Pia-Maria}, title = {Might the cargo of extracellular vesicles constitute a biological link between psychosocial stress and osteoporosis?}, series = {Psychoneuroendocrinology / International Society of Psychoneuroendocrinology}, volume = {131}, journal = {Psychoneuroendocrinology / International Society of Psychoneuroendocrinology}, number = {Supplement}, publisher = {Elsevier}, address = {Oxford}, issn = {0306-4530}, doi = {10.1016/j.psyneuen.2021.105480}, pages = {1}, year = {2021}, abstract = {Background: Osteoporosis is a growing public health problem. It is known that stress-related diseases such as depression may impair bone quality and lead to osteoporosis. The association between psychosocial stress and bone health may be triggered by alterations of mitochondrial function and cell signaling and intercellular communication. In this context, extracellular vesicles (EVs) may be relevant due to their crucial role in intercellular communicators through the transfer of cargo. Aim: This narrative review aims to summarize if the cargo of extracellular vesicles can constitute a biological link between psychosocial stress and osteoporosis. Methods: To evaluate this research question, a thorough literature search was conducted using PubMed, Google Scholar, and Science Direct. The research keywords are allostatic load, bone remodeling, microRNA, osteoblast, and osteoclast. A total of 21 articles were included in the narrative review. Results: We found that certain miRNAs in EVs, including miR-126a-3p, miR-128-3p, and miR-187-5p, have been described as crucial players in both psychosocial stress and osteoporosis. Discussion: This review describes EVs and their cargo as a potential mediator linking psychosocial stress and osteoporosis for the first time by highlighting common crucial miRNAs. However, based on the included studies, it is unclear whether EV-mediated transport of biological cargoes can alter the function of target cells in a real physiological environment.}, language = {en} } @article{HeWuertzKozakKuehletal.2021, author = {He, Yangyang and W{\"u}rtz-Kozak, Karin and K{\"u}hl, Linn Kristina and Wippert, Pia-Maria}, title = {Extracellular vesicles}, series = {International journal of molecular sciences}, volume = {22}, journal = {International journal of molecular sciences}, number = {11}, publisher = {Molecular Diversity Preservation International}, address = {Basel}, issn = {1422-0067}, doi = {10.3390/ijms22115846}, pages = {15}, year = {2021}, abstract = {Osteoporosis is characterized by low bone mass and damage to the bone tissue's microarchitecture, leading to increased fracture risk. Several studies have provided evidence for associations between psychosocial stress and osteoporosis through various pathways, including the hypothalamic-pituitary-adrenocortical axis, the sympathetic nervous system, and other endocrine factors. As psychosocial stress provokes oxidative cellular stress with consequences for mitochondrial function and cell signaling (e.g., gene expression, inflammation), it is of interest whether extracellular vesicles (EVs) may be a relevant biomarker in this context or act by transporting substances. EVs are intercellular communicators, transfer substances encapsulated in them, modify the phenotype and function of target cells, mediate cell-cell communication, and, therefore, have critical applications in disease progression and clinical diagnosis and therapy. This review summarizes the characteristics of EVs, their role in stress and osteoporosis, and their benefit as biological markers. We demonstrate that EVs are potential mediators of psychosocial stress and osteoporosis and may be beneficial in innovative research settings.}, language = {en} }