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    Inhibition of CD44 intracellular domain production suppresses bovine articular chondrocyte de-differentiation induced by excessive mechanical stress loading

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    Author
    Sobue, Yasumori; Takahashi, Nobunori; Ohashi, Yoshifumi; Suzuki, Mochihito; Nishiume, Tsuyoshi; Kobayakawa, Tomonori; Terabe, Kenya; Knudson, Warren; Knudson, Cheryl; Ishiguro, Naoki; Kojima, Toshihisa
    Abstract
    CD44 fragmentation is enhanced in chondrocytes of osteoarthritis (OA) patients. We hypothesized that mechanical stress-induced enhancement of CD44-intracellular domain (CD44-ICD) production plays an important role in the de-differentiation of chondrocytes and OA. This study aimed to assess the relationship between CD44-ICD and chondrocyte gene expression. Monolayer cultured primary bovine articular chondrocytes (BACs) were subjected to cyclic tensile strain (CTS) loading. ADAM10 inhibitor (GI254023X) and γ-secretase inhibitor (DAPT) were used to inhibit CD44 cleavage. In overexpression experiments, BACs were electroporated with a plasmid encoding CD44-ICD. CTS loading increased the expression of ADAM10 and subsequent CD44 cleavage, while decreasing the expression of SOX9, aggrecan, and type 2 collagen (COL2). Overexpression of CD44-ICD also resulted in decreased expression of these chondrocyte genes. Both GI254023X and DAPT reduced the production of CD44-ICD upon CTS loading, and significantly rescued the reduction of SOX9 expression by CTS loading. Chemical inhibition of CD44-ICD production also rescued aggrecan and COL2 expression following CTS loading. Our findings suggest that CD44-ICD is closely associated with the de-differentiation of chondrocytes. Excessive mechanical stress loading promoted the de-differentiation of BACs by enhancing CD44 cleavage and CD44-ICD production. Suppression of CD44 cleavage has potential as a novel treatment strategy for OA.
    URI
    http://hdl.handle.net/10342/8122
    Date
    2019-10-17
    Citation:
    APA:
    Sobue, Yasumori, & Takahashi, Nobunori, & Ohashi, Yoshifumi, & Suzuki, Mochihito, & Nishiume, Tsuyoshi, & Kobayakawa, Tomonori, & Terabe, Kenya, & Knudson, Warren, & Knudson, Cheryl, & Ishiguro, Naoki, & Kojima, Toshihisa. (October 2019). Inhibition of CD44 intracellular domain production suppresses bovine articular chondrocyte de-differentiation induced by excessive mechanical stress loading. Scientific Reports, (14901. Retrieved from http://hdl.handle.net/10342/8122

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    MLA:
    Sobue, Yasumori, and Takahashi, Nobunori, and Ohashi, Yoshifumi, and Suzuki, Mochihito, and Nishiume, Tsuyoshi, and Kobayakawa, Tomonori, and Terabe, Kenya, and Knudson, Warren, and Knudson, Cheryl, and Ishiguro, Naoki, and Kojima, Toshihisa. "Inhibition of CD44 intracellular domain production suppresses bovine articular chondrocyte de-differentiation induced by excessive mechanical stress loading". Scientific Reports. . (14901.), October 2019. February 26, 2021. http://hdl.handle.net/10342/8122.
    Chicago:
    Sobue, Yasumori and Takahashi, Nobunori and Ohashi, Yoshifumi and Suzuki, Mochihito and Nishiume, Tsuyoshi and Kobayakawa, Tomonori and Terabe, Kenya and Knudson, Warren and Knudson, Cheryl and Ishiguro, Naoki and Kojima, Toshihisa, "Inhibition of CD44 intracellular domain production suppresses bovine articular chondrocyte de-differentiation induced by excessive mechanical stress loading," Scientific Reports 9, no. (October 2019), http://hdl.handle.net/10342/8122 (accessed February 26, 2021).
    AMA:
    Sobue, Yasumori, Takahashi, Nobunori, Ohashi, Yoshifumi, Suzuki, Mochihito, Nishiume, Tsuyoshi, Kobayakawa, Tomonori, Terabe, Kenya, Knudson, Warren, Knudson, Cheryl, Ishiguro, Naoki, Kojima, Toshihisa. Inhibition of CD44 intracellular domain production suppresses bovine articular chondrocyte de-differentiation induced by excessive mechanical stress loading. Scientific Reports. October 2019; 9() 14901. http://hdl.handle.net/10342/8122. Accessed February 26, 2021.
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