Matrix stiffening related lncRNA SNHG8 regulates chemosensitivity of ovarian cancer / 生物医学工程学杂志

Extracellular matrix (ECM) has been implicated in tumor progress and chemosensitivity. Ovarian cancer brings a great threat to the health of women with a significant feature of high mortality and poor prognosis. However, the potential significance of matrix stiffness in the pattern of long non-coding RNAs (lncRNAs) expression and ovarian cancer drug sensitivity is still largely unkown. Here, based on RNA-seq data of ovarian cancer cell cultured on substrates with different stiffness, we found that a great amount of lncRNAs were upregulated in stiff group, whereas SNHG8 was significantly downregulated, which was further verified in ovarian cancer cells cultured on polydimethylsiloxane (PDMS) hydrogel. Knockdown of SNHG8 led to an impaired efficiency of homologous repair, and decreased cellular sensitivity to both etoposide and cisplatin. Meanwhile, the results of the GEPIA analysis indicated that the expression of SNHG8 was significantly decreased in ovarian cancer tissues, which was negatively correlated with the overall survival of patients with ovarian cancer. In conclusion, matrix stiffening related lncRNA SNHG8 is closely related to chemosensitivity and prognosis of ovarian cancer, which might be a novel molecular marker for chemotherapy drug instruction and prognosis prediction.

Research progress of chondrocyte mechanotransduction mediated by TRPV4 and PIEZOs / 生物医学工程学杂志

Mechanical signal transduction are crucial for chondrocyte in response to mechanical cues during the growth, development and osteoarthritis (OA) of articular cartilage. Extracellular matrix (ECM) turnover regulates the matrix mechanical microenvironment of chondrocytes. Thus, understanding the mechanotransduction mechanisms during chondrocyte sensing the matrix mechanical microenvironment can develop effective targeted therapy for OA. In recent decades, growing evidences are rapidly advancing our understanding of the mechanical force-dependent cartilage remodeling and injury responses mediated by TRPV4 and PIEZOs. In this review, we highlighted the mechanosensing mechanism mediated by TRPV4 and PIEZOs during chondrocytes sensing mechanical microenvironment of the ECM. Additionally, the latest progress in the regulation of OA by inflammatory signals mediated by TRPV4 and PIEZOs was also introduced. These recent insights provide the potential mechanotheraputic strategies to target these channels and prevent cartilage degeneration associated with OA. This review will shed light on the pathogenesis of articular cartilage, searching clinical targeted therapies, and designing cell-induced biomaterials.

Single Cell Traction Force Measured by Foldable Microplates / 医用生物力学

Objective To fabricate a foldable microplate for single cell culture and establish finite element model of the folding microplate, so as to calculate traction force of single cells during contraction in three-dimensional (3D) state.Methods The folding angle of the microplate casued by cell traction force was calculated. Then the relation between bending moment and folding angle as well as the relation between traction force and bending moment were derived by using finite element simulation, so as to realize the characterization of traction force for singel cell in 3D state.Results The folding angles of the microplate with HSF and MC3T3-E1 cells in 3D state were 73°-173° and 49°-138°, respectively. The single cell traction forces of HSF and MC3T3-E1 cells were 55-210 nN and 52-161 nN, respectively.Conclusions The proposed method for measuring traction force of single cells in 3D state by fabricating the foldable microplate for single cell culture will provide some references for further development of calculating traction forces in 3D cell adhesion, spreading and migration.

Deeper Understanding the Pathogenesis of Osteoarthritis from Matrix Viscoelasticity and Calcium Signaling / 医用生物力学

Generally, extracellular matrix (ECM) has the characteristics of viscoelasticity. In osteoarthritis (OA), catabolic processes alter the viscoelastic properties of functional pericellular matrix (PCM) of chondrocytes. Chondrocytes sense and respond to their mechanical microenvironment via an array of mechanosensitive receptors and channels that activate a complex network of downstream signaling pathways to regulate several cell processes central to OA pathology. Advances in understanding the specific mechanosignalling mechanisms in articular cartilage will promote the development of cell microenvironment construction in cartilage tissue engineering and the targeted precision therapeutics for OA. In this review, the work on the mechanism of matrix viscoelasticity regulating chondrocytes mechanotransduction by Agarwal et al. was briefly commented, and the recent advances related with their work was also discussed.

Paracrine effect of chondrocytes on gene expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in osteoblasts / 中国组织工程研究

BACKGROUND:Cel co-culture can maximize the simulation ofin vivomicroenvironment. Cel scratch test and interleukin-1β can destroy the balance between matrix metaloproteinases (MMPs) and matrix metaloproteinase inhibitors (TIMPs), resulting in extracelular matrix degradation of the articular cartilage, functional disorders of chondrocytes and articular cartilage degeneration. OBJECTIVE:To study the effect of interleukin-1β on migration, MMP and TIMP expression of chondrocytes co-cultured with osteoblast supernatantin vitro. METHODS:There were three groups: chondrocyte monoculture group, osteoblast+chondrocyte group (co-culture group), osteoblast+chondrocyte+interleukin-1β group (interleukin-1β group). Cel scratch test was conducted to observe the migration of chondrocytes within 24 hours. Semi-quantitative PCR test was used to detect the changes in expressions of MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1, TIMP-2, TIMP-3, TIMP-9 in chondrocytes within 24 hours. RESULTS AND CONCLUSION:Compared with the monoculture group, cel migration rate of the other two groups were increased significantly (P< 0.01). Compared with the monoculture group, the gene expressions of MMP-1, MMP-2, MMP-3 and MMP-9 were increased significantly in the coculture group (P < 0. 05); the gene expressions of MMP-1, MMP-3, MMP-9 were increased significantly in the interleukin-1β group (P< 0. 01). Compared with monoculture group, the gene expression of TIMP-1 was increased significantly (P < 0. 01), but the gene expressions of TIMP-3 and TIMP-4 were declined significantly (P < 0. 05) in the other two groups. These findings indicate that co-culture of chondrocytes with osteoblasts can promote chondrocytes migration, enhance gene expression of chondrocytes MMP-1, MMP-2, MMP-3, MMP-9 and regulate gene expression of TIMPs family. Interleukin-1β inhibitsthe migration of chondrocytes co-cultured with osteoblasts and gene expression of TIMPs family.