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  • 1
    In: FASEB BioAdvances, Wiley, Vol. 5, No. 12 ( 2023-12), p. 541-557
    Kurzfassung: Mustn1 , a gene expressed exclusively in the musculoskeletal system, was shown in previous in vitro studies to be a key regulator of myogenic differentiation and myofusion. Other studies also showed Mustn1 expression associated with skeletal muscle development and hypertrophy. However, its specific role in skeletal muscle function remains unclear. This study sought to investigate the effects of Mustn1 in a conditional knockout (KO) mouse model in Pax7 positive skeletal muscle satellite cells. Specifically, we investigated the potential effects of Mustn1 on myogenic gene expression, grip strength, alterations in gait, ex vivo investigations of isolated skeletal muscle isometric contractions, and potential changes in the composition of muscle fiber types. Results indicate that Mustn1 KO mice did not present any substantial phenotypic changes or significant variations in genes related to myogenic differentiation and fusion. However, an approximately 10% decrease in overall grip strength was observed in the 2‐month‐old KO mice in comparison to the control wild type (WT), but this decrease was not significant when normalized by weight. KO mice also generated approximately 8% higher vertical force than WT at 4 months in the hindlimb. Ex vivo experiments revealed decreases in about 20 to 50% in skeletal muscle contractions and about 10%–20% fatigue in soleus of both 2‐ and 4‐month‐old KO mice, respectively. Lastly, immunofluorescent analyses showed a persistent increase of Type IIb fibers up to 15‐fold in the KO mice while Type I fibers decreased about 20% and 30% at both 2 and 4 months, respectively. These findings suggest a potential adaptive or compensatory mechanism following Mustn1 loss, as well as hinting at an association between Mustn1 and muscle fiber typing. Collectively, Mustn1 's complex roles in skeletal muscle physiology requires further research, particularly in terms of understanding the potential role of Mustn1 in muscle repair and regeneration, as well as with influence of exercise. Collectively, these will offer valuable insights into Mustn1 's key biological functions and regulatory pathways.
    Materialart: Online-Ressource
    ISSN: 2573-9832 , 2573-9832
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2023
    ZDB Id: 2969880-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    Online-Ressource
    Online-Ressource
    The Company of Biologists ; 2022
    In:  Journal of Experimental Biology Vol. 225, No. 19 ( 2022-10-01)
    In: Journal of Experimental Biology, The Company of Biologists, Vol. 225, No. 19 ( 2022-10-01)
    Kurzfassung: The ability to securely grasp substrates of variable diameter is critical to arboreal animals. Arboreal specialists have emerged across several vertebrate lineages – including mammals, lizards and amphibians – and several attempts have been made to quantify their grasping performance, by measuring either gripping (i.e. forces generated about an object or substrate enclosed within the digits) or pulling (i.e. the ability to resist being removed from a substrate) forces. In this study, we present data on both pulling and gripping performance across a range of substrate diameters (0.5–17.5 mm) within a model parrot species (Agapornis roseicollis). Parrots represent an ancient arboreal lineage, allowing us to compare their abilities with those of arboreal specialists within other tetrapod groups. Data were collected using 3D-printed perches of variable diameter, and forces were registered using either an AMTI low-load force plate (grip force) or a Harvard Apparatus portable strength tester (pull force). Gripping forces peaked at a 5 mm diameter perch, while pulling forces were greatest at a 2.5 mm diameter. All forces strongly diminished above 10 mm size, suggesting grip force is optimized when utilizing small perches, a finding which corresponds to observational studies of preferential perching habits among free-ranging parrots. Relative grasping performance (adjusted for body size) in parrots is roughly equivalent to that of other arboreal specialists from other tetrapod lineages, but low when compared with that of raptorial birds that utilize their feet during aerial prey capture. Further taxonomic sampling is encouraged to contextualize how grasping performance varies in an adaptive evolutionary context.
    Materialart: Online-Ressource
    ISSN: 0022-0949 , 1477-9145
    Sprache: Englisch
    Verlag: The Company of Biologists
    Publikationsdatum: 2022
    ZDB Id: 1482461-9
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    In: Journal of the American Geriatrics Society, Wiley, Vol. 71, No. 8 ( 2023-08), p. 2640-2652
    Kurzfassung: Medication‐related osteonecrosis of the jaw (MRONJ) is clinically defined as a non‐healing jawbone ulcerative‐necrotic lesion appearing after dental therapy or minor trauma in patients treated previously with anti‐resorptive, anti‐angiogenic or immunomodulators. Older patients with osteoporosis and cancer receive these pharmacological agents regularly. As these patients are long‐term survivors, efficient treatment is of paramount importance for their quality of life. Methods Literature searches via PubMed were conducted to identify relevant MRONJ studies. Basic information on MRONJ classification, clinical features, and pathosphysiology is presented herein as well as various clinical studies dealing with MRONJ in patients with osteoporosis and cancer. Lastly, we discuss current managment of patients and new trends in treatment of MRONJ. Results Although close follow‐up and local hygiene have been advocated by some authors, severe forms of MRONJ are not responsive to conservative therapy. At present, there is no “gold standard” therapy for this condition. However, as the physiopathological basis of MRONJ is represented by the anti‐angiogenic action of various pharmacological agents, new methods to increase and promote local angiogenesis and vascularization have recently been successfully tested in vitro, limited preclinical studies, and in a pilot clinical study. Conclusions It appears that the best method implies application on the lesion of endothelial progenitor cells as well as pro‐angiogenic factors such as Vascular Endothelial Growth Factor (VEGF) and other related molecules. More recently, scaffolds in which these factors have been incorporated have shown positive results in limited trials. However, these studies must be replicated to include a large number of cases before any official therapeutic protocol is adopted.
    Materialart: Online-Ressource
    ISSN: 0002-8614 , 1532-5415
    URL: Issue
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2023
    ZDB Id: 2040494-3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    Online-Ressource
    Online-Ressource
    Wiley ; 2010
    In:  Journal of Cellular Biochemistry Vol. 111, No. 2 ( 2010-10), p. 295-309
    In: Journal of Cellular Biochemistry, Wiley, Vol. 111, No. 2 ( 2010-10), p. 295-309
    Kurzfassung: We previously identified osteoactivin (OA) as a novel secreted osteogenic factor with high expression in developing long bones and calvaria, and that stimulates osteoblast differentiation and matrix mineralization in vitro. In this study, we report on OA mRNA and protein expression in intact long bone and growth plate, and in fracture calluses collected at several time points up to 21 days post‐fracture (PF). OA mRNA and protein were highly expressed in osteoblasts localized in the metaphysis of intact tibia, and in hypertrophic chondrocytes localized in growth plate, findings assessed by in situ hybridization and immunohistochemistry, respectively. Using a rat fracture model, Northern blot analysis showed that expression of OA mRNA was significantly higher in day‐3 and day‐10 PF calluses than in intact rat femurs. Using in situ hybridization, we examined OA mRNA expression during fracture healing and found that OA was temporally regulated, with positive signals seen as early as day‐3 PF, reaching a maximal intensity at day‐10 PF, and finally declining at day‐21 PF. At day‐5 PF, which correlates with chondrogenesis, OA mRNA levels were significantly higher in the soft callus than in intact femurs. Similarly, we detected high OA protein immunoexpression throughout the reparative phase of the hard callus compared to intact femurs. Interestingly, the secreted OA protein was also detected within the newly made cartilage matrix and osteoid tissue. Taken together, these results suggest the possibility that OA plays an important role in bone formation and serves as a positive regulator of fracture healing. J. Cell. Biochem. 111: 295–309, 2010. © 2010 Wiley‐Liss, Inc.
    Materialart: Online-Ressource
    ISSN: 0730-2312 , 1097-4644
    URL: Issue
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2010
    ZDB Id: 1479976-5
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
    Online-Ressource
    Online-Ressource
    Wiley ; 2018
    In:  Journal of Polymer Science Part A: Polymer Chemistry Vol. 56, No. 6 ( 2018-03-15), p. 635-644
    In: Journal of Polymer Science Part A: Polymer Chemistry, Wiley, Vol. 56, No. 6 ( 2018-03-15), p. 635-644
    Kurzfassung: Amphiphilic cationic poly(ethylene oxide)‐ S (polylysine)‐poly( d , l ‐lactide) (mPEO‐S(CK n )‐PLA) tri‐arm star copolymers were synthesized by a combination of ring opening polymerization (ROP) and a thiol–disulfide exchange. The mPEO‐S(CK n )‐PLA copolymers were found to be non‐cytotoxic and could effectively condense GFP plasmid DNA into nanometer‐sized complexes, as characterized by dynamic light scattering (DLS), suitable for endocytotic cellular uptake. In vitro DNA transfection studies showed that the amphiphilic structure is capable of DNA transfection and GFP expression. Addition of chloroquine into the medium further enhanced the DNA transfection efficiency. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56 , 635–644
    Materialart: Online-Ressource
    ISSN: 0887-624X , 1099-0518
    URL: Issue
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2018
    ZDB Id: 3004641-5
    ZDB Id: 1473076-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
    In: Biomaterials, Elsevier BV, Vol. 32, No. 31 ( 2011-11), p. 7831-7838
    Materialart: Online-Ressource
    ISSN: 0142-9612
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 2011
    ZDB Id: 2004010-6
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
    Online-Ressource
    Online-Ressource
    American Scientific Publishers ; 2016
    In:  Journal of Biomedical Nanotechnology Vol. 12, No. 6 ( 2016-06-01), p. 1285-1296
    In: Journal of Biomedical Nanotechnology, American Scientific Publishers, Vol. 12, No. 6 ( 2016-06-01), p. 1285-1296
    Materialart: Online-Ressource
    ISSN: 1550-7033
    Sprache: Englisch
    Verlag: American Scientific Publishers
    Publikationsdatum: 2016
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
    Online-Ressource
    Online-Ressource
    Wiley ; 2007
    In:  Journal of Bone and Mineral Research Vol. 22, No. 3 ( 2007-03), p. 366-374
    In: Journal of Bone and Mineral Research, Wiley, Vol. 22, No. 3 ( 2007-03), p. 366-374
    Kurzfassung: HIF‐1α activates genes under hypoxia and was hypothesized to regulate bone regeneration. Surprisingly, HIF‐1α +/− fracture calluses are larger, stronger, and stiffer than HIF‐1α +/+ calluses because of decreased apoptosis. These data identify apoptosis inhibition as a means to enhance bone regeneration. Introduction: Bone regeneration subsequent to fracture involves the synergistic activation of multiple signaling pathways. Localized hypoxia after fracture activates hypoxia‐inducible factor 1α (HIF‐1α), leading to increased expression of HIF‐1 target genes. We therefore hypothesized that HIF‐1α is a key regulator of bone regeneration. Materials and Methods: Fixed femoral fractures were generated in mice with partial HIF‐1α deficiency (HIF‐1α +/− ) and wildtype littermates (HIF‐1α +/+ ). Fracture calluses and intact contralateral femurs from postfracture days (PFDs) 21 and 28 ( N = 5–10) were subjected to μCT evaluation and four‐point bending to assess morphometric and mechanical properties. Molecular analyses were carried out on PFD 7, 10, and 14 samples ( N = 3) to determine differential gene expression at both mRNA and protein levels. Finally, TUNEL staining was performed on PFD 14 samples ( N = 2) to elucidate differential apoptosis. Results: Surprisingly, fracture calluses from HIF‐1α +/− mice exhibited greater mineralization and were larger, stronger, and stiffer. Microarray analyses focused on hypoxia‐induced genes revealed differential expression (between genotypes) of several genes associated with the apoptotic pathway. Real‐time PCR confirmed these results, showing higher expression of proapoptotic protein phosphatase 2a (PP2A) and lower expression of anti‐apoptotic B‐cell leukemia/lymphoma 2 (BCL2) in HIF‐1α +/+ calluses. Subsequent TUNEL staining showed that HIF‐1α +/+ calluses contained larger numbers of TUNEL + chondrocytes and osteoblasts than HIF‐1α +/− calluses. Conclusions: We conclude that partial HIF‐1α deficiency results in decreased chondrocytic and osteoblastic apoptosis, thereby allowing the development of larger, stiffer calluses and enhancing bone regeneration. Furthermore, apoptosis inhibition may be a promising target for developing new treatments to accelerate bone regeneration.
    Materialart: Online-Ressource
    ISSN: 0884-0431 , 1523-4681
    RVK:
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2007
    ZDB Id: 2008867-X
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
    Online-Ressource
    Online-Ressource
    Wiley ; 2014
    In:  Journal of Bone and Mineral Research Vol. 29, No. 11 ( 2014-11), p. 2307-2322
    In: Journal of Bone and Mineral Research, Wiley, Vol. 29, No. 11 ( 2014-11), p. 2307-2322
    Kurzfassung: The complexity of fracture repair makes it an ideal process for studying the interplay between the molecular, cellular, tissue, and organ level events involved in tissue regeneration. Additionally, as fracture repair recapitulates many of the processes that occur during embryonic development, investigations of fracture repair provide insights regarding skeletal embryogenesis. Specifically, inflammation, signaling, gene expression, cellular proliferation and differentiation, osteogenesis, chondrogenesis, angiogenesis, and remodeling represent the complex array of interdependent biological events that occur during fracture repair. Here we review studies of bone regeneration in genetically modified mouse models, during aging, following environmental exposure, and in the setting of disease that provide insights regarding the role of multipotent cells and their regulation during fracture repair. Complementary animal models and ongoing scientific discoveries define an increasing number of molecular and cellular targets to reduce the morbidity and complications associated with fracture repair. Last, some new and exciting areas of stem cell research such as the contribution of mitochondria function, limb regeneration signaling, and microRNA (miRNA) posttranscriptional regulation are all likely to further contribute to our understanding of fracture repair as an active branch of regenerative medicine. © 2014 American Society for Bone and Mineral Research.
    Materialart: Online-Ressource
    ISSN: 0884-0431 , 1523-4681
    URL: Issue
    RVK:
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2014
    ZDB Id: 2008867-X
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
    Online-Ressource
    Online-Ressource
    Wiley ; 2019
    In:  Journal of Bone and Mineral Research Vol. 34, No. 5 ( 2019-05), p. 797-809
    In: Journal of Bone and Mineral Research, Wiley, Vol. 34, No. 5 ( 2019-05), p. 797-809
    Kurzfassung: The repair of a fractured bone is critical to the well‐being of humans. Failure of the repair process to proceed normally can lead to complicated fractures, exemplified by either a delay in union or a complete nonunion. Both of these conditions lead to pain, the possibility of additional surgery, and impairment of life quality. Additionally, work productivity decreases, income is reduced, and treatment costs increase, resulting in financial hardship. Thus, developing effective treatments for these difficult fractures or even accelerating the normal physiological repair process is warranted. Accumulating evidence shows that microRNAs (miRNAs), small noncoding RNAs, can serve as key regulatory molecules of fracture repair. In this review, a brief description of the fracture repair process and miRNA biogenesis is presented, as well as a summary of our current knowledge of the involvement of miRNAs in physiological fracture repair, osteoporotic fractures, and bone defect healing. Further, miRNA polymorphisms associated with fractures, miRNA presence in exosomes, and miRNAs as potential therapeutic orthobiologics are also discussed. This is a timely review as several miRNA‐based therapeutics have recently entered clinical trials for nonskeletal applications and thus it is incumbent upon bone researchers to explore whether miRNAs can become the next class of orthobiologics for the treatment of skeletal fractures.
    Materialart: Online-Ressource
    ISSN: 0884-0431 , 1523-4681
    URL: Issue
    RVK:
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2019
    ZDB Id: 2008867-X
    Standort Signatur Einschränkungen Verfügbarkeit
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