Browsing by Subject "Bone"

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  • Alyodawi, Khalid; Vermeij, Wilbert P.; Omairi, Saleh; Kretz, Oliver; Hopkinson, Mark; Solagna, Francesca; Joch, Barbara; Brandt, Renata M. C.; Barnhoorn, Sander; van Vliet, Nicole; Ridwan, Yanto; Essers, Jeroen; Mitchell, Robert; Morash, Taryn; Pasternack, Arja; Ritvos, Olli; Matsakas, Antonios; Collins-Hooper, Henry; Huber, Tobias B.; Hoeijmakers, Jan H. J.; Patel, Ketan (2019)
    Background One of the principles underpinning our understanding of ageing is that DNA damage induces a stress response that shifts cellular resources from growth towards maintenance. A contrasting and seemingly irreconcilable view is that prompting growth of, for example, skeletal muscle confers systemic benefit. Methods To investigate the robustness of these axioms, we induced muscle growth in a murine progeroid model through the use of activin receptor IIB ligand trap that dampens myostatin/activin signalling. Progeric mice were then investigated for neurological and muscle function as well as cellular profiling of the muscle, kidney, liver, and bone. Results We show that muscle of Ercc1(Delta/-) progeroid mice undergoes severe wasting (decreases in hind limb muscle mass of 40-60% compared with normal mass), which is largely protected by attenuating myostatin/activin signalling using soluble activin receptor type IIB (sActRIIB) (increase of 30-62% compared with untreated progeric). sActRIIB-treated progeroid mice maintained muscle activity (distance travel per hour: 5.6 m in untreated mice vs. 13.7 m in treated) and increased specific force (19.3 mN/mg in untreated vs. 24.0 mN/mg in treated). sActRIIb treatment of progeroid mice also improved satellite cell function especially their ability to proliferate on their native substrate (2.5 cells per fibre in untreated progeroids vs. 5.4 in sActRIIB-treated progeroids after 72 h in culture). Besides direct protective effects on muscle, we show systemic improvements to other organs including the structure and function of the kidneys; there was a major decrease in the protein content in urine (albumin/creatinine of 4.9 sActRIIB treated vs. 15.7 in untreated), which is likely to be a result in the normalization of podocyte foot processes, which constitute the filtration apparatus (glomerular basement membrane thickness reduced from 224 to 177 nm following sActRIIB treatment). Treatment of the progeric mice with the activin ligand trap protected against the development of liver abnormalities including polyploidy (18.3% untreated vs. 8.1% treated) and osteoporosis (trabecular bone volume; 0.30 mm(3) in treated progeroid mice vs. 0.14 mm(3) in untreated mice, cortical bone volume; 0.30 mm(3) in treated progeroid mice vs. 0.22 mm(3) in untreated mice). The onset of neurological abnormalities was delayed (by similar to 5 weeks) and their severity reduced, overall sustaining health without affecting lifespan. Conclusions This study questions the notion that tissue growth and maintaining tissue function during ageing are incompatible mechanisms. It highlights the need for future investigations to assess the potential of therapies based on myostatin/activin blockade to compress morbidity and promote healthy ageing.
  • Waller, Benjamin; Munukka, Matti; Multanen, Juhani; Rantalainen, Timo; Poyhonen, Tapani; Nieminen, Miika T.; Kiviranta, Ilkka; Kautiainen, Hannu; Selanne, Harri; Dekker, Joost; Sipila, Sarianna; Kujala, Urho M.; Hakkinen, Arja; Heinonen, Ari (2013)
  • Bourgery, Matthieu; Ekholm, Erika; Fagerlund, Katja; Hiltunen, Ari; Puolakkainen, Tero; Pursiheimo, Juha-Pekka; Heino, Terhi; Määttä, Jorma; Heinonen, Jussi; Yatkin, Emrah; Laitala, Tiina; Säämänen, Anna-Marja (2021)
    Long-bone fracture is a common injury and its healing process at the fracture site involves several overlapping phases, including inflammation, migration of mesenchymal progenitors into the fracture site, endochondral ossification, angiogenesis and finally bone remodelling. Increasing evidence shows that small noncoding RNAs are important regulators of chondrogenesis, osteogenesis and fracture healing. MicroRNAs are small singlestranded, non-coding RNA-molecules intervening in most physiological and biological processes, including fracture healing. Angiogenin-cleaved 5' tRNA halves, also called as tiRNAs (stress-induced RNAs) have been shown to repress protein translation. In order to gain further understanding on the role of small noncoding RNAs in fracture healing, genome wide expression profiles of tiRNAs, miRNAs and mRNAs were followed up to 14 days after fracture in callus tissue of an in vivo mouse model with closed tibial fracture and, compared to intact bone and articular cartilage at 2 months of age. Total tiRNA expression level in cartilage was only approximately one third of that observed in control D0 bone. In callus tissue, 11 mature 5 ' end tiRNAs out of 191 tiRNAs were highly expressed, and seven of them were differentially expressed during fracture healing. When comparing the control tissues, 25 miRNAs characteristic to bone and 29 miRNAs characteristic to cartilage tissue homeostasis were identified. Further, a total of 54 out of 806 miRNAs and 5420 out of 18,700 mRNAs were differentially expressed (DE) in callus tissue during fracture healing and, in comparison to control bone. They were associated to gene ontology processes related to mesenchymal tissue development and differentiation. A total of 581 miRNA-mRNA interactions were identified for these 54 DE miRNAs by literature searches in PubMed, thereby linking by Spearman correlation analysis 14 downregulated and 28 upregulated miRNAs to 164 negatively correlating and 168 positively correlating miRNA-mRNA pairs with chondrogenic and osteogenic phases of fracture healing. These data indicated that tiRNAs and miRNAs were differentially expressed in fracture callus tissue, suggesting them important physiological functions during fracture healing. Hence, the data provided by this study may contribute to future clinical applications, such as potential use as biomarkers or as tools in the development of novel therapeutic approaches for fracture healing.
  • Li, Lyra (Helsingfors universitet, 2016)
    The aim of this thesis is to analyse Chinese and Chinese American womanhood and women’s experiences through comparing the portrayal of mother-daughter relationships in Amy Tan’s The Joy Luck Club and Fae Myenne Ng’s Bone. By situating both novels in the context of Asian American literary and immigration history, I employ deconstructionist criticism to question binary oppositions of gender and nativism/assimilation representations in the novels. The thesis is structured according to separate analyses on how mother-daughter relationships influence and are shaped by Chinese immigrant mothers and their American-born daughters. In the chapter on mothers, I argue that the different women’s consciousness is manifested as maternal practices and the desire to articulate their own experiences in a marginalising society. The chapter on daughters focuses on the impact conflicting Chinese and American cultural frameworks have on the daughters, who need to continuously renegotiate their self-identity. While The Joy Luck Club and Bone share common themes of generational discord and the significance of retaining a cultural and ethnic identity, they differ in tone and agenda. Whereas The Joy Luck Club focuses on feminist reinvention and empowerment through a matrilineal descent, Bone explores family dysfunctions in the context of larger sociocultural issues pertaining to Chinese immigration in the US. This is further emphasised by the inclusion of Chinese male experiences in Bone. I conclude that in The Joy Luck Club and Bone, mother-daughter relationships highlight the tension between independent and intersubjective identity negotiations, illustrated particularly through the themes of storytelling and memory. Binary oppositions of Chinese and Chinese American identities are deconstructed through interpreting women’s social and cultural experiences as fluid and hybrid, thus demonstrating the need for more convoluted, even conflicting, representations of gender and identity differences.
  • Mäkinen, Lauri (Helsingfors universitet, 2016)
    Rab23:n vaikutukset intramembranoottiseen luutumiseen ovat olleet tunnetut 2000-luvun alusta, mutta geenin täsmälliset vaikutukset endokondraalisten luiden kehitykselle ovat yhä osittain epäselvät. Tämän tutkielman tavoitteena on havainnoida ja dokumentoida Rab23^opb2-genotyypin vaikutukset pitkien luiden fenotyyppiin käyttäen aineistona 15,5-18,5 sikiövuorokautisten hiirten olka- ja reisiluita ja menetelminä histokemiallisia värjäyksiä sekä in situ hybridisaatiota. Tutkimuksessa havaittiin Rab23^opb2-mutaation vaikuttavan hiirten olkaluiden kokonaispituuteen (p<0,05) sekä mineralisoituneen korteksin (p<0,05) ja distaalisen proliferoivan vyöhykkeen pituuksiin. Lisäksi kondrosyyttien maturaatiossa havaittiin epäjärjestäytyneisyyttä reservin kondrosyyttien muuntuessa proliferoiviksi. Löydökset sopivat yhteen aiemman tutkimuksen kanssa, jonka perusteella Rab23:n tiedetään osallistuvan hedgehog-signaloinnin säätelyyn. Sen sijaan havainto kondrosyyttien maturaation epäjärjestäytyneisyydestä voi olla riippumaton hedgehog-signaloinnista. Aihe edellyttää jatkotutkimuksia.