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Inhibition of CD44 intracellular domain production suppresses bovine articular chondrocyte de-differentiation induced by excessive mechanical stress loading.
Sobue, Yasumori; Takahashi, Nobunori; Ohashi, Yoshifumi; Suzuki, Mochihito; Nishiume, Tsuyoshi; Kobayakawa, Tomonori; Terabe, Kenya; Knudson, Warren; Knudson, Cheryl; Ishiguro, Naoki; Kojima, Toshihisa.
Afiliación
  • Sobue Y; Nagoya University Graduate School of Medicine, Department of Orthopedic Surgery, 65 Tsurumai, Showa, Nagoya, 466-8550, Japan.
  • Takahashi N; Nagoya University Graduate School of Medicine, Department of Orthopedic Surgery, 65 Tsurumai, Showa, Nagoya, 466-8550, Japan. nobunori@med.nagoya-u.ac.jp.
  • Ohashi Y; Nagoya University Graduate School of Medicine, Department of Orthopedic Surgery, 65 Tsurumai, Showa, Nagoya, 466-8550, Japan.
  • Suzuki M; Nagoya University Graduate School of Medicine, Department of Orthopedic Surgery, 65 Tsurumai, Showa, Nagoya, 466-8550, Japan.
  • Nishiume T; Nagoya University Graduate School of Medicine, Department of Orthopedic Surgery, 65 Tsurumai, Showa, Nagoya, 466-8550, Japan.
  • Kobayakawa T; Kobayakawa Clinic, Department of Orthopedic Surgery, 1969 Kuno, Fukuroi, 437-0061, Japan.
  • Terabe K; Nagoya University Graduate School of Medicine, Department of Orthopedic Surgery, 65 Tsurumai, Showa, Nagoya, 466-8550, Japan.
  • Knudson W; The Brody School of Medicine, East Carolina University, 600 Moye Boulevard, Greenville, NC 27834-4354, North Carolina, USA.
  • Knudson C; The Brody School of Medicine, East Carolina University, 600 Moye Boulevard, Greenville, NC 27834-4354, North Carolina, USA.
  • Ishiguro N; Nagoya University Graduate School of Medicine, Department of Orthopedic Surgery, 65 Tsurumai, Showa, Nagoya, 466-8550, Japan.
  • Kojima T; Nagoya University Graduate School of Medicine, Department of Orthopedic Surgery, 65 Tsurumai, Showa, Nagoya, 466-8550, Japan.
Sci Rep ; 9(1): 14901, 2019 10 17.
Article en En | MEDLINE | ID: mdl-31624271
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteoartritis / Cartílago Articular / Receptores de Hialuranos / Condrocitos / Desdiferenciación Celular Límite: Animals / Humans / Male Idioma: En Revista: Sci Rep Año: 2019 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteoartritis / Cartílago Articular / Receptores de Hialuranos / Condrocitos / Desdiferenciación Celular Límite: Animals / Humans / Male Idioma: En Revista: Sci Rep Año: 2019 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido