ACLT led to a disorganization of the collagen framework at the early stage of OA development, which decreases the mechanical resistance of the menisci. GAG content increases in response to this degradation. All of these results demonstrate the strong correlation between matrix and mechanical alterations.
Congenital spine deformities may be influenced by movements
in utero
, but the effects of foetal immobility on spine and rib development remain unclear. The purpose of the present study was to determine (1) critical time-periods when rigid paralysis caused the most severe disruption in spine and rib development and (2) how the effects of an early, short-term immobilisation were propagated to the different features of spine and rib development. Chick embryos were immobilised once per single embryonic day (E) between E3 and E6 and harvested at E9. To assess the ontogenetic effects following single-day immobilisation, other embryos were immobilised at E4 and harvested daily between E5 and E9. Spinal curvature, vertebral shape and segmentation and rib development were analysed by optical projection tomography and histology. The results demonstrated that periods critical for movement varied for different aspects of spine and rib development. Single-day immobilisation at E3 or E4 resulted in the most pronounced spinal curvature abnormalities, multiple wedged vertebrae and segmentation defects, while single-day immobilisation at E5 led to the most severe rib abnormalities. Assessment of ontogenetic effects following single-day immobilisation at E4 revealed that vertebral segmentation defects were subsequent to earlier vertebral body shape and spinal curvature abnormalities, while rib formation (although delayed) was independent from thoracic vertebral shape or curvature changes.
A day-long immobilisation in chicks severely affected spine and rib development, highlighting the importance of abnormal foetal movements at specific time-points and motivating targeted prenatal monitoring for early diagnosis of congenital scoliosis.
Embryonic muscle forces are necessary for normal vertebral development and spinal curvature, but their involvement in intervertebral disc (IVD) development remains unclear. The aim of the current study was to determine how muscle contractions affect (1) notochord involution and vertebral segmentation, and (2) IVD development including the mechanical properties and morphology, as well as collagen fibre alignment in the annulus fibrosus. Muscular dysgenesis (mdg) mice were harvested at three prenatal stages: at Theiler Stage (TS)22 when notochord involution starts, at TS24 when involution is complete, and at TS27 when the IVD is formed. Vertebral and IVD development were characterised using histology, immunofluorescence, and indentation testing. The results revealed that notochord involution and vertebral segmentation occurred independently of muscle contractions between TS22 and TS24. However, in the absence of muscle contractions, we found vertebral fusion in the cervical region at TS27, along with (i) a displacement of the nucleus pulposus towards the dorsal side, (ii) a disruption of the structural arrangement of collagen in the annulus fibrosus, and (iii) an increase in viscous behaviour of the annulus fibrosus. These findings emphasise the important role of mechanical forces during IVD development, and demonstrate a critical role of muscle loading during development to enable proper annulus fibrosus formation. They further suggest a need for mechanical loading in the creation of fibre-reinforced tissue engineering replacement IVDs as a therapy for IVD degeneration.
In the ACLT model, weight-bearing stress was modified in the ZOI. This disruption of the stress pattern induced alterations of the tissues composing the bone-cartilage unit. In term of mechanical properties, all tissues exhibited changes. The most affected tissue was the most superficial: hyaline cartilage displayed the strongest relative decrease (42%) followed by calcified cartilage (37%) and cortical plate was slightly modified (16%). This supports the hypotheses that PTOA initiates in the hyaline cartilage.
The mechanical properties of the extracellular matrix are essential for regulating cancer cell behaviour, but how they change depending on tumour type remains unclear. The aim of the current study was to determine how the mechanical properties of tumours that frequently metastasize to bones were affected depending on histological type. Human breast, kidney, and thyroid specimens containing tumour and normal tissue were collected during surgery. The elastic modulus and elastic fraction of each sample were characterised using atomic force microscopy and compared with histopathological markers. We observed that tumour mechanical properties were differentially affected depending on organ and histological type. Indeed, clear cell renal carcinoma and poorly differentiated thyroid carcinoma displayed a decrease in the elastic modulus compared to their normal counterpart, while breast tumours, papillary renal carcinoma and fibrotic thyroid tumours displayed an increase in the elastic modulus. Elastic fraction decreased only for thyroid tumour tissue, indicating an increase in the viscosity. These findings suggest a unique mechanical profile associated with each subtype of cancer. Therefore, viscosity could be a discriminator between tumour and normal thyroid tissue, while elasticity could be a discriminator between the subtypes of breast, kidney and thyroid cancers.
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