Responses of apoptosis and matrix metabolism of annulus fibrosus cells to different magnitudes of mechanical tension in vitro

Abstract

Background: Annulus fibrosus (AF) is important to confine disc nucleus pulposus (NP) tissue during mechanical load experience. However, the knowledge on AF cell biology under mechanical load is much limited compared with disc NP. Objective: The present study aimed to investigate responses of apoptosis and matrix metabolism of AF cells to different magnitudes of mechanical tension in vitro. Methods: Rat AF cells were subjected to different magnitudes (5, 10, and 20% elongations at a frequency of 1.0 Hz for 6 h per day) of mechanical tension for 7 days. Control AF cells were cultured without mechanical tension. Cell apoptosis ratio, caspase-3 activity, gene/protein expression of apoptosis-related molecules (Bcl-2, Bax, caspase-3/cleaved caspase-3 and cleaved PARP), matrix macromolecules (aggrecan and collagen I) and matrix metabolism-related enzymes (TIMP-1, TIMP-3, MMP-3, and ADAMTS-4) were analyzed. Results: Compared with 5% tension group and control group, 10 and 20% tension groups significantly increased apoptosis ratio, caspase-3 activity, up-regulated gene/protein expression of Bax, caspase-3/cleaved caspase-3, cleaved PARP, MMP-3, and ADAMTS-4, whereas down-regulated gene/protein expression of Bcl-2, aggrecan, collagen I, TIMP-1, and TIMP-3. No significant difference was found in these parameters apart from Bcl-2 expression between the control group and 5% tension group. Conclusion: High mechanical tension promotes AF cell apoptosis and suppresses AF matrix synthesis compared with low mechanical tension. The present study indirectly indicates how mechanical overload induces disc degeneration through affecting AF biology.

High glucose promotes annulus fibrosus cell apoptosis through activating the JNK and p38 MAPK pathways

“…Cells of the AF tissue originate from mesenchyme and present many features similar to fibroblasts and chondrocytes [10,11]. AF cells help to maintain the structural integrity through synthesizing and secreting normal and adequate extracellular matrix, whereas some intrinsic and extrinsic pathways activated by the detrimental pathological factors often induce AF cell apoptosis [12,13]. In the previous animal disc degeneration models [12,14], the number of apoptotic AF cells is significantly increased, indicating that AF cell apoptosis is promoted and involved in the progression of disc degeneration.…”

Rosuvastatin: A Potential Therapeutic Agent for Inhibition of Mechanical Pressure-Induced Intervertebral Disc Degeneration

“…Ao et al 16 are in agreement with us in that they found in a bipedal standing-induced IDD model that MP significantly activated the HIF-1α/NF-κB signaling pathway, leading to restricted proliferation of NPCs and extracellular matrix (mainly COL2A1) degradation increase, which in turn leads to IDD. Jiang et al 17 made similar findings by treating fibrocystic ring cells with different deformation rates of draw mechanical stress. Their results showed that a deformation rate of 5% was not sufficient to affect the phenotype of fibrous ring cells, but when the deformation rate was increased from 10% to 20%, the phenotype of the cells was significantly altered with the increase in deformation rate.…”

Aberrant mechanical loading induces annulus fibrosus cells apoptosis in intervertebral disc degeneration via mechanosensitive ion channel Piezo1

“…A human AF tissue level analysis exhibited that the tensile hoop stress can reach 12.7 MPa [13]. Several studies have verified the apoptosis of AFCs significantly rises with the elevation of aberrant mechanical loading degree [7,[14][15][16]. Therapies that inhibit aberrant mechanical loading-induced AFCs apoptosis can result in alleviated IVDD in animal experiments [17,18].…”