scholarly journals Age-related changes in microRNAs expression in cruciate ligaments of wild-stock house mice

2021 ◽  
Author(s):  
Yalda Ashraf Kharaz ◽  
Katarzyna Goljanek Whysall ◽  
Gareth Nye ◽  
Jane Hurst ◽  
Anne Mcardle ◽  
...  

Aim: Cruciate ligaments (CLs) of the knee joint are commonly injured following trauma or ageing. MicroRNAs (miRs) are potential therapeutic targets in musculoskeletal disorders. This study aimed to 1) identify if wild-stock house (WSH) mice are an appropriate model to study age-related changes of the knee joint and 2) investigate expression of miRs in ageing murine CLs. Methods: Knee joints were collected from 6 and 24 months old C57BL/6 and WSH mice (Mus musculus domesticus) for histological analysis. RNA extraction and qPCR gene expression were performed on CLs in 6, 12, 24, and 30 month WSH old mice. Expression of miR targets in CLs was determined, followed by analysis of predicted mRNA target genes and Ingenuity Pathway Analysis. Results: Higher CL and knee OARSI histological scores were found in 24 month old WSH mice compared to 6 and 12 month old C57BL/6 and 6 month old WSH mice (p< 0.05). miR-29a and miR-34a were upregulated in 30 month-old WSH mice in comparison to 6, 12 and 24-month-old WSH mice (p<0.05). Ingenuity Pathway Analysis on miR-29a and 34a targets was associated with inflammation through interleukins, TGFβ and Notch genes and p53 signalling. Collagen type I alpha 1 chain (COL1A1) correlated negatively with both miR-29a (r= -0.35) and miR-34a (r= -0.33). Conclusion: The findings of this study support WSH house mice as an accelerated ageing model of the murine knee joint. This study also indicated that miR-29a and 34a may be important regulators of COL1A1 gene expression in murine CLs.

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 141-141
Author(s):  
Joseph Gordon III ◽  
Nicholas Remillard ◽  
Chad Straight ◽  
Rajakumar Nagarajan ◽  
Bruce Damon ◽  
...  

Abstract Decreases in muscle size and function are a general consequence of old age; the precise mechanisms of these changes remain unclear. Recent studies suggest that fat deposition in muscle may also contribute to dysfunction in older adults. Fat content was quantified in the quadriceps, and its effects on function in healthy young (21-45 y) and older (65-75 y) men and women (n=44) of comparable physical activity were compared. A subset of the young matched with the older group for muscle fat content were also examined. Peak fat-free whole muscle cross-sectional area (mCSA; cm2), volume (MV; cm3), fat content (fat fraction, FF; %), specific torque (Nm/mCSA) and peak contraction velocity (Nm∙s-1) were determined using fat-water magnetic resonance imaging and dynamometry (0-300□∙s-1). To examine potential molecular mechanisms of muscle weakness, vastus lateralis biopsies were obtained (n=31) and cross-bridge kinetics of type I and II fibers were determined. FF was higher in older adults than young (8.4±1.2% (SE), 7.6±1.4; p=0.03), while mCSA (48.9±10.4 vs. 64.2±17.3), MV (1536±532 vs. 2112±708), specific torque (2.6±0.4 vs. 3.2±0.4), and peak voluntary contraction velocity (422±20 vs. 441±23) were lower in older than young (p&lt;0.01). Type II fiber myosin attachment rate was slower and attachment time longer in older muscle (p&lt;0.017), providing a potential mechanism for the slowing of peak contraction velocity with age. Notably, differences at the whole muscle and molecular levels remained for the subset of young and older groups matched for FF, suggesting that fat deposition in muscle does not exacerbate age-related changes in function.


2008 ◽  
Vol 294 (6) ◽  
pp. E1160-E1168 ◽  
Author(s):  
Elena Silvestri ◽  
Assunta Lombardi ◽  
Pieter de Lange ◽  
Luigi Schiavo ◽  
Antonia Lanni ◽  
...  

Aging is associated with changes in thyroid gland physiology. Age-related changes in the contribution of peripheral tissues to thyroid hormone serum levels have yet to be systematically assessed. Here, we investigated age-related alterations in the contributions of the liver and kidney to thyroid hormone homeostasis using 6-, 12-, and 24-mo-old male Wistar rats. A significant and progressive decline in plasma thyroxine occurred with age, but triiodothyronine (T3) was decreased only at 24 mo. This was associated with an unchanged protein level of the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) in the kidney and with a decreased MCT8 level in the liver at 24 mo. Hepatic type I deiodinase (D1) protein level and activity declined progressively with age. Renal D1 levels were decreased at both 12 and 24 mo but D1 activity was decreased only at 24 mo. In the liver, no changes occurred in thyroid hormone receptor (TR) TRα1, whereas a progressive increase in TRβ1 occurred at both mRNA and total protein levels. In the kidney, both TRα1 and TRβ1 mRNA and total protein levels were unchanged between 6 and 12 mo but increased at 24 mo. Interestingly, nuclear TRβ1 levels were decreased in both liver and kidney at 12 and 24 mo, whereas nuclear TRα1 levels were unchanged. Collectively, our data show differential age-related changes among hepatic and renal MCT8 and D1 and TR expressions, and they suggest that renal D1 activity is maintained with age to compensate for the decrease in hepatic T3 production.


Metabolism ◽  
1995 ◽  
Vol 44 (3) ◽  
pp. 320-324 ◽  
Author(s):  
Stephen J. Giddings ◽  
Lynn R. Carnaghi ◽  
Arshag D. Mooradian

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Ian R Lanza ◽  
Daniel K Short ◽  
Kevin R Short ◽  
Yan W Asmann ◽  
Sreekumar Raghavakaimal ◽  
...  

Author(s):  
Michaël J. A. Girard ◽  
Jun-Kyo F. Suh ◽  
Michael Bottlang ◽  
Claude F. Burgoyne ◽  
J. Crawford Downs

The sclera is the outer shell and principal load-bearing tissue of the eye, which consists primarily of avascular lamellae of collagen fibers. Ninety percent of the collagen fibers in the sclera are Type I, which provide the eye with necessary mechanical strength to sustain intraocular pressure (IOP). In the posterior sclera, there is a fenestrated canal, called the optic nerve head (ONH), through which the retinal ganglion cell axons pass transmitting visual signals from the retina to the brain. The opening of the ONH is structurally supported by a fenestrated connective tissue called the lamina cribrosa.


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