Sex differences in heel pad stiffness during in vivo loading and unloading

The proteoglycan-containing pericellular matrix (PCM) controls both the biophysical and biochemical microenvironment of osteocytes, which are the most abundant cells embedded and dispersed in bones. As a molecular sieve, osteocytic PCMs not only regulate mass transport to and from osteocytes but also act as sensors of external mechanical environments. The turnover of osteocytic PCM remains largely unknown due to technical challenges. Here, we report a novel imaging technique based on metabolic labeling and “click-chemistry,” which labels de novo PCM as “halos” surrounding osteocytes in vitro and in vivo. We then tested the method and showed different labeling patterns in young vs. old bones. Further “pulse-chase” experiments revealed dramatic difference in the “half-life” of PCM of cultured osteocytes (~70 h) and that of osteocytes in vivo (~75 d). When mice were subjected to either 3-week hindlimb unloading or 7-week tibial loading (5.1 N, 4 Hz, 3 d/week), PCM half-life was shortened (~20 d) and degradation accelerated. Matrix metallopeptidase MMP-14 was elevated in mechanically loaded osteocytes, which may contribute to PCM degradation. This study provides a detailed procedure that enables semi-quantitative study of the osteocytic PCM remodeling in vivo and in vitro.

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Gender and Sex Are Key Determinants in Osteoarthritis Not Only Confounding Variables. A Systematic Review of Clinical Data

Journal of Clinical Medicine ◽

10.3390/jcm10143178 ◽

2021 ◽

Vol 10 (14) ◽

pp. 3178

Author(s):

Matilde Tschon ◽

Deyanira Contartese ◽

Stefania Pagani ◽

Veronica Borsari ◽

Milena Fini

Keyword(s):

Health Care ◽

Sex Differences ◽

Ex Vivo ◽

Case Series ◽

Cartilage Volume ◽

Review Literature ◽

Care Needs ◽

Clinical Pain

Many risk factors for osteoarthritis (OA) have been noted, while gender/sex differences have been understated. The work aimed to systematically review literature investigating as primary aim the relationship between gender/sex related discriminants and OA. The search was performed in PubMed, Science Direct and Web of Knowledge in the last 10 years. Inclusion criteria were limited to clinical studies of patients affected by OA in any joints, analyzing as primary aim gender/sex differences. Exclusion criteria were review articles, in vitro, in vivo and ex vivo studies, case series studies and papers in which gender/sex differences were adjusted as confounding variable. Of the 120 records screened, 42 studies were included. Different clinical outcomes were analyzed: morphometric differences, followed by kinematics, pain, functional outcomes after arthroplasty and health care needs of patients. Women appear to use more health care, have higher OA prevalence, clinical pain and inflammation, decreased cartilage volume, physical difficulty, and smaller joint parameters and dimensions, as compared to men. No in-depth studies or mechanistic studies analyzing biomarker differential expressions, molecular pathways and omic profiles were found that might drive preclinical and clinical research towards sex-/gender-oriented protocols.

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Blood pressure regulation V: in vivo mechanical properties of precapillary vessels as affected by long-term pressure loading and unloading

European Journal of Applied Physiology ◽

10.1007/s00421-013-2758-9 ◽

2013 ◽

Vol 114 (3) ◽

pp. 499-509 ◽

Cited By ~ 7

Author(s):

Ola Eiken ◽

Igor B. Mekjavic ◽

Roger Kölegård

Keyword(s):

Mechanical Properties ◽

Blood Pressure ◽

Blood Pressure Regulation ◽

Pressure Regulation ◽

Pressure Loading ◽

Loading And Unloading

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Fundamental Roles of Axial Stretch in Isometric and Isobaric Evaluations of Vascular Contractility

Journal of Biomechanical Engineering ◽

10.1115/1.4042171 ◽

2019 ◽

Vol 141 (3) ◽

Cited By ~ 4

Author(s):

Alexander W. Caulk ◽

Jay D. Humphrey ◽

Sae-Il Murtada

Keyword(s):

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Muscle Function ◽

Contractile Function ◽

Contractile Activity ◽

Comparison Of Methods ◽

Axial Stretch ◽

Smooth Muscle Function ◽

In Vivo Loading

Vascular smooth muscle cells (VSMCs) can regulate arterial mechanics via contractile activity in response to changing mechanical and chemical signals. Contractility is traditionally evaluated via uniaxial isometric testing of isolated rings despite the in vivo environment being very different. Most blood vessels maintain a locally preferred value of in vivo axial stretch while subjected to changes in distending pressure, but both of these phenomena are obscured in uniaxial isometric testing. Few studies have rigorously analyzed the role of in vivo loading conditions in smooth muscle function. Thus, we evaluated effects of uniaxial versus biaxial deformations on smooth muscle contractility by stimulating two regions of the mouse aorta with different vasoconstrictors using one of three testing protocols: (i) uniaxial isometric testing, (ii) biaxial isometric testing, and (iii) axially isometric plus isobaric testing. Comparison of methods (i) and (ii) revealed increased sensitivity and contractile capacity to potassium chloride and phenylephrine (PE) with biaxial isometric testing, and comparison of methods (ii) and (iii) revealed a further increase in contractile capacity with isometric plus isobaric testing. Importantly, regional differences in estimated in vivo axial stretch suggest locally distinct optimal biaxial configurations for achieving maximal smooth muscle contraction, which can only be revealed with biaxial testing. Such differences highlight the importance of considering in vivo loading and geometric configurations when evaluating smooth muscle function. Given the physiologic relevance of axial extension and luminal pressurization, we submit that, when possible, axially isometric plus isobaric testing should be employed to evaluate vascular smooth muscle contractile function.

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P2245Sex differences in the in-vivo markers of platelet activation among patients with ischemic heart disease: insights from the EVA study

European Heart Journal ◽

10.1093/eurheartj/ehz748.0723 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

V Raparelli ◽

G F Romiti ◽

N Sperduti ◽

G F Santangelo ◽

M Vano ◽

...

Keyword(s):

Coronary Artery Disease ◽

Acute Coronary Syndrome ◽

Sex Differences ◽

Coronary Artery ◽

Coronary Stenosis ◽

Clinical Presentation ◽

Coronary Syndrome ◽

Chronic Angina ◽

Artery Disease

Abstract Background/Introduction Ischemic heart diseases (IHD) are not synonymous with obstructive flow-limiting coronary artery disease (CAD), especially in women. Platelet dysfunction is suggested as a potential mechanism favouring ischemia in non-obstructive CAD. However, it is unknown whether sex differences in platelet function of patients with non-obstructive CAD exist. Purpose We assessed for sex differences in in-vivo markers of platelet activation among patients with the acute coronary syndrome and chronic stable angina, with or without obstructive CAD Methods From the “Endocrine Vascular disease Approach” (EVA) study, we selected IHD patients undergoing urgent or elective coronary angiography with complete baseline clinical characteristics and angiographic data. Non-obstructive CAD was defined as the presence of coronary stenosis <50%. Thromboxane B2 (TxB2) and soluble P-selectin (sP-s) were measured at baseline. A sex-stratified analysis of platelet biomarkers was performed. Results Among two-hundred-seventy-seven patients (mean age 67±11, 37% women), non-obstructive CAD was documented in 25% of patients. Acute coronary syndrome (ACS) was the reason for angiography in 61% of cases. Women had more frequently ACS, as compared with men (54.8% vs 41.3%, p=0.001), with predominantly non-obstructive CAD. Median serum TxB2 (121.5 [92.7–174.0] vs 103.5 [83.0–140.2] pg/ml, p=0.005) and plasma sP-s (27.0 [18.7–35.0] vs 22.0 [16.0–30.0] ng/ml, p=0.006) levels were higher in patients with ACS as compared with the ones with stable chronic angina. The median concentration of TxB2 was significantly increased in women as compared with men, regardless of the clinical presentation and the coronary stenosis degree (all comparison, p<0.001). However, women with non-obstructive CAD were the group with the highest serum levels of TxB2 (140.0 [111.0–152.0] pg/ml). Sex differences in the plasma sP-s level were also observed among patients with stable chronic angina (women, 26 [20.0–34.0] vs men, 21 [16.6–27.7] ng/ml, p=0.002) and with non-obstructive CAD (women, 26 [20.5–34.5] vs men, 18.5 [16.6–26.0] ng/ml, p=0.003). Conclusion(s) Women with IHD and non-obstructive CAD had increased level of TxB2 and sP-s as compared with men, independently by the clinical presentation. Further investigations are warranted to verify the role of platelet hyperactivation in the pathogenesis of myocardial ischemia with non-obstructive coronary artery disease among women. Acknowledgement/Funding Scientific Independence of Young Researchers Program (RBSI14HNVT) - Ministry of Education, University and Research (MIUR)

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Assessment of in vivo loading history of the patellofemoral joint: a study combining patellar position, tilt, alignment and bone SPECT/CT

Knee Surgery Sports Traumatology Arthroscopy ◽

10.1007/s00167-013-2698-2 ◽

2013 ◽

Vol 22 (12) ◽

pp. 3039-3046 ◽

Cited By ~ 20

Author(s):

Stephan N. Schön ◽

Faik K. Afifi ◽

Helmut Rasch ◽

Felix Amsler ◽

Niklaus F. Friederich ◽

...

Keyword(s):

Patellofemoral Joint ◽

Loading History ◽

Patellar Position ◽

History Of ◽

Bone Spect ◽

In Vivo Loading

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Investigation on the load-displacement curves of a human healthy heel pad: In vivo compression data compared to numerical results

Medical Engineering & Physics ◽

10.1016/j.medengphy.2011.12.013 ◽

2012 ◽

Vol 34 (9) ◽

pp. 1253-1259 ◽

Cited By ~ 39

Author(s):

C.G. Fontanella ◽

S. Matteoli ◽

E.L. Carniel ◽

J.E. Wilhjelm ◽

A. Virga ◽

...

Keyword(s):

Numerical Results ◽

Heel Pad ◽

Compression Data ◽

Load Displacement

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SPECT/CT Assessment of In-Vivo Loading of the Knee Correlates with Polyethylene Deformation in Retrieved Total Knee Arthroplasty

Tomography ◽

10.3390/tomography8010015 ◽

2022 ◽

Vol 8 (1) ◽

pp. 180-188

Author(s):

Harry Hothi ◽

Arianna Cerquiglini ◽

Lukas Büel ◽

Johann Henckel ◽

Lukas B. Moser ◽

...

Keyword(s):

Distribution Patterns ◽

Tracer Uptake ◽

Medial Compartment ◽

Lateral Side ◽

Imaging Data ◽

Total Knee Replacements ◽

Knee Replacements ◽

Total Knee ◽

In Vivo Loading

Background: SPECT/CT distribution patterns in patients with total knee replacements have previously been correlated with factors such as time of implantation, implant type and alignment. It is unknown, however, if an increased and more extended bone tracer uptake (BTU) in SPECT/CT, representing loading of the joint, correlates with findings from retrieval studies. The aim of this study was to further understand this subject. Materials and Methods: 62 retrieved TKA were included. SPECT/CT was performed prior to revision. Quantitative and qualitative medio-lateral comparisons of BTU intensity and distribution in the tibia were performed. Retrieval analysis was performed with a micro-CT method to assess the thickness differences between medial and lateral sides of polyethylene inserts with symmetrical designs. Results: In the subgroup of TKA with asymmetrical SPECT/CT distribution, there was a significant correlation between retrieval and medical imaging data (p = 0.0355): patients showing a more extended BTU in the medial compartment also had a significantly thinner insert in the medial compartment, and vice versa in the lateral side. Conclusion: This is the first study comparing BTU distribution patterns and retrieval findings. Our results support the hypothesis that SPECT/CT is able to identify bone activity due to implant position and loading.

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Long-term depression of excitatory transmission in the lateral septum

Journal of Neurophysiology ◽

10.1152/jn.00657.2019 ◽

2021 ◽

Author(s):

Chanchanok Chaichim ◽

Madeleine Jessica Radnan ◽

Gadiel Dumlao ◽

John M. Power

Keyword(s):

Sex Differences ◽

Drugs Of Abuse ◽

Brain Slices ◽

Lateral Septum ◽

Network Activity ◽

Excitatory Postsynaptic Potential ◽

Glutamatergic Transmission ◽

Long Term Depression

Neurons in the lateral septum (LS) integrate glutamatergic synaptic inputs, primarily from hippocampus, and send inhibitory projections to brain regions involved in reward and the generation of motivated behavior. Motivated learning and drugs of abuse have been shown to induce long-term changes in the strength of glutamatergic synapses in the LS, but the cellular mechanisms underlying long-term synaptic modification in the LS are poorly understood. Here we examined synaptic transmission and long-term depression (LTD) in brain slices prepared from male and female C57BL/6 mice. No sex differences were observed in whole-cell patch-clamp recordings of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA-R) and N-methyl-D-aspartate receptor (NMDA-R) mediated currents. Low frequency stimulation of the fimbria fibre bundle (1 Hz 15 min) induced LTD of the LS field excitatory postsynaptic potential (fEPSP). Induction of LTD was blocked by the NMDA-R antagonist APV, but not the selective antagonist of GluN2B-containing NMDA-R ifenprodil. These results demonstrate the NMDA-R dependence of LTD in the LS. The LS is a sexually dimorphic structure and sex differences in glutamatergic transmission have been reported in vivo; our results suggest sex differences observed in vivo result from network activity rather than intrinsic differences in glutamatergic transmission.

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