Hypoxia Potentiates Anabolic Effects of Exogenous Hyaluronic Acid in Rat Articular Cartilage

被引：14

作者：

Ichimaru, Shohei ^{[1
]}

Nakagawa, Shuji ^{[1
]}

Arai, Yuji ^{[2
]}

Kishida, Tsunao ^{[3
]}

Shin-Ya, Masaharu ^{[3
]}

Honjo, Kuniaki ^{[1
]}

Tsuchida, Shinji ^{[1
]}

Inoue, Hiroaki ^{[1
]}

Fujiwara, Hiroyoshi ^{[1
]}

Shimomura, Seiji ^{[1
]}

Mazda, Osam ^{[3
]}

Kubo, Toshikazu ^{[1
]}

机构：

[1] Kyoto Prefectural Univ Med, Grad Sch Med Sci, Dept Orthopaed, Kamigyo Ku, Kawaramachi Hirokoji, Kyoto 6028566, Japan

[2] Kyoto Prefectural Univ Med, Grad Sch Med Sci, Dept Sports & Para Sports Med, Kamigyo Ku, Kawaramachi Hirokoji, Kyoto 6028566, Japan

[3] Kyoto Prefectural Univ Med, Grad Sch Med Sci, Dept Immunol, Kamigyo Ku, Kawaramachi Hirokoji, Kyoto 6028566, Japan

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2016年 / 17卷 / 07期

关键词：

hypoxia-inducible factor 1; hyaluronic acid; CD44; articular cartilage; extracellular matrix; CELL-SURFACE RECEPTOR; ENDOCHONDRAL OSSIFICATION; OSTEOARTHRITIS; CHONDROCYTES; KNEE; CD44; SOX9; REDIFFERENTIATION; HIF-1-ALPHA; EXPRESSION;

D O I：

10.3390/ijms17071013

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Hyaluronic acid (HA) is used clinically to treat osteoarthritis (OA), but its pharmacological effects under hypoxic conditions remain unclear. Articular chondrocytes in patients with OA are exposed to a hypoxic environment. This study investigated whether hypoxia could potentiate the anabolic effects of exogenous HA in rat articular cartilage and whether these mechanisms involved HA receptors. HA under hypoxic conditions significantly enhanced the expression of extracellular matrix genes and proteins in explant culture, as shown by real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and dimethylmethylene blue (DMMB) assays. Staining with Safranin-O and immunohistochemical staining with antibody to type II collagen were also enhanced in pellet culture. The expression of CD44 was increased by hypoxia and significantly suppressed by transfection with siRNAs targeting hypoxia-inducible factor 1 alpha (siHIF-1). These findings indicate that hypoxia potentiates the anabolic effects of exogenous HA by a mechanism in which HIF-1 positively regulates the expression of CD44, enhancing the binding affinity for exogenous HA. The anabolic effects of exogenous HA may increase as OA progresses.

引用

页数：12

共 37 条

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