Mechanotransduction in meniscus fibrochondrocytes: What about caveolae?

Vyhlidal, Margaret J; Adesida, Adetola B

doi:10.1002/jcp.30616

Cited by 5 publications

(4 citation statements)

References 43 publications

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“…Furthermore, the mechanotransduction function of FOSB in MFCs ( Szojka et al, 2021a ) was reported by Szojka et al, and its function in the IL-17 signalling pathway was well demonstrated ( Benderdour et al, 2002 ). Finally, Vyhlidal et al recognized the potential of caveolae molecules such as CAV1/2 in the mechanotransductive mechanism of the meniscus, but this needs to be further verified in future studies ( Vyhlidal and Adesida, 2021 ). The transcriptome changes are summarized in Table 4 .…”

Section: Resultsmentioning

confidence: 99%

Engineered Human Meniscus in Modeling Sex Differences of Knee Osteoarthritis in Vitro

Kunze

et al. 2022

Front. Bioeng. Biotechnol.

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Background: Osteoarthritis (OA) primarily affects mechanical load-bearing joints. The knee joint is the most impacted by OA. Knee OA (KOA) occurs in almost all demographic groups, but the prevalence and severity are disproportionately higher in females. The molecular mechanism underlying the pathogenesis and progression of KOA is unknown. The molecular basis of biological sex matters of KOA is not fully understood. Mechanical stimulation plays a vital role in modulating OA-related responses of load-bearing tissues. Mechanical unloading by simulated microgravity (SMG) induced OA-like gene expression in engineered cartilage, while mechanical loading by cyclic hydrostatic pressure (CHP), on the other hand, exerted a pro-chondrogenic effect. This study aimed to evaluate the effects of mechanical loading and unloading via CHP and SMG, respectively, on the OA-related profile changes of engineered meniscus tissues and explore biological sex-related differences.Methods: Tissue-engineered menisci were made from female and male meniscus fibrochondrocytes (MFCs) under static conditions of normal gravity in chondrogenic media and subjected to SMG and CHP culture. Constructs were assayed via histology, immunofluorescence, GAG/DNA assays, RNA sequencing, and testing of mechanical properties.Results: The mRNA expression of ACAN and COL2A1, was upregulated by CHP but downregulated by SMG. COL10A1, a marker for chondrocyte hypertrophy, was downregulated by CHP compared to SMG. Furthermore, CHP increased GAG/DNA levels and wet weight in both female and male donors, but only significantly in females. From the transcriptomics, CHP and SMG significantly modulated genes related to the ossification, regulation of ossification, extracellular matrix, and angiogenesis Gene Ontology (GO) terms. A clear difference in fold-change magnitude and direction was seen between the two treatments for many of the genes. Furthermore, differences in fold-change magnitudes were seen between male and female donors within each treatment. SMG and CHP also significantly modulated genes in OA-related KEGG pathways, such as mineral absorption, Wnt signalling pathway, and HIF-1 signalling pathway.Conclusion: Engineered menisci responded to CHP and SMG in a sex-dependent manner. SMG may induce an OA-like profile, while CHP promotes chondrogenesis. The combination of SMG and CHP could serve as a model to study the early molecular events of KOA and potential drug-targetable pathways.

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Section: Resultsmentioning

confidence: 99%

Engineered Human Meniscus in Modeling Sex Differences of Knee Osteoarthritis in Vitro

Kunze

et al. 2022

Front. Bioeng. Biotechnol.

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“…This type of collagen fibers was also the main component in the outer region of the native meniscus [ 33 ]. It can assist meniscus to resist against circumferential tension and extrusion during suffering load [ 34 ]. The lack of collagen I may cause the function loss in resisting tensile load in the outer and intermedia region of meniscus.…”

Section: Discussionmentioning

confidence: 99%

The triply periodic minimal surface-based 3D printed engineering scaffold for meniscus function reconstruction

Wang

Jin

et al. 2022

Biomater Res

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Background The meniscus injury is a common disease in the area of sports medicine. The main treatment for this disease is the pain relief, rather than the meniscal function recovery. It may lead to a poor prognosis and accelerate the progression of osteoarthritis. In this study, we designed a meniscal scaffold to achieve the purposes of meniscal function recovery and cartilage protection. Methods The meniscal scaffold was designed using the triply periodic minimal surface (TPMS) method. The scaffold was simulated as a three-dimensional (3D) intact knee model using a finite element analysis software to obtain the results of different mechanical tests. The mechanical properties were gained through the universal machine. Finally, an in vivo model was established to evaluate the effects of the TPMS-based meniscal scaffold on the cartilage protection. The radiography and histological examinations were performed to assess the cartilage and bony structures. Different regions of the regenerated meniscus were tested using the universal machine to assess the biomechanical functions. Results The TPMS-based meniscal scaffold with a larger volume fraction and a longer functional periodicity demonstrated a better mechanical performance, and the load transmission and stress distribution were closer to the native biomechanical environment. The radiographic images and histological results of the TPMS group exhibited a better performance in terms of cartilage protection than the grid group. The regenerated meniscus in the TPMS group also had similar mechanical properties to the native meniscus. Conclusion The TPMS method can affect the mechanical properties by adjusting the volume fraction and functional periodicity. The TPMS-based meniscal scaffold showed appropriate features for meniscal regeneration and cartilage protection.

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Section: Introductionmentioning

confidence: 99%

“…Understanding the structural and mechanical cues that guide communication between a cell and its surrounding extracellular matrix (ECM) to promote regeneration is critical. 6 Further, a model that mimics the native mechanical properties of the knee meniscus is required to understand this mechanotransducive signaling. The native equilibrium compressive modulus from human cadaveric meniscus tissue ranges from 50 to 1048 kPa, differing significantly across regions of the tissue.…”

Section: Introductionmentioning

confidence: 99%

Modulating pentenoate‐functionalized hyaluronic acid hydrogel network properties for meniscal fibrochondrocyte mechanotransduction

Burkey

Castillo

Elrod

et al. 2023

J Biomedical Materials Res

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Knee meniscus tears are one of the most common musculoskeletal injuries. While meniscus replacements using allografts or biomaterial‐based scaffolds are available, these treatments rarely result in integrated, functional tissue. Understanding mechanotransducive signaling cues that promote a meniscal cell regenerative phenotype is critical to developing therapies that promote tissue regeneration rather than fibrosis after injury. The purpose of this study was to develop a hyaluronic acid (HA) hydrogel system with tunable crosslinked network properties by modulating the degree of substitution (DoS) of reactive‐ene groups to investigate mechanotransducive cues received by meniscal fibrochondrocytes (MFCs) from their microenvironment. A thiol‐ene step‐growth polymerization crosslinking mechanism was employed using pentenoate‐functionalized hyaluronic acid (PHA) and dithiothreitol to achieve tunability of the chemical crosslinks and resulting network properties. Increased crosslink density, reduced swelling, and increased compressive modulus (60–1020 kPa) were observed with increasing DoS. Osmotic deswelling effects were apparent in PBS and DMEM+ compared to water; swelling ratios and compressive moduli were decreased in the ionic buffers. Frequency sweep studies showed storage and loss moduli of hydrogels at 1 Hz approach reported meniscus values and showed increasing viscous response with increasing DoS. The degradation rate increased with decreasing DoS. Lastly, modulating PHA hydrogel surface modulus resulted in control of MFC morphology, suggesting relatively soft hydrogels (E = 60 ± 35 kPa) promote more inner meniscus phenotype compared to rigid hydrogels (E = 610 ± 66 kPa). Overall, these results highlight the use of ‐ene DoS modulation in PHA hydrogels to tune crosslink density and physical properties to understand mechanotransduction mechanisms required to promote meniscus regeneration.

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Mechanotransduction in meniscus fibrochondrocytes: What about caveolae?

Cited by 5 publications

References 43 publications

Engineered Human Meniscus in Modeling Sex Differences of Knee Osteoarthritis in Vitro

Engineered Human Meniscus in Modeling Sex Differences of Knee Osteoarthritis in Vitro

The triply periodic minimal surface-based 3D printed engineering scaffold for meniscus function reconstruction

Modulating pentenoate‐functionalized hyaluronic acid hydrogel network properties for meniscal fibrochondrocyte mechanotransduction

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