Targeting mitochondrial responses to intra-articular fracture to prevent posttraumatic osteoarthritis

被引：99

作者：

Coleman, Mitchell C. ^{[1
]}

Goetz, Jessica E. ^{[1
]}

Brouillette, Marc J. ^{[1
]}

Seol, Dongrim ^{[1
]}

Willey, Michael C. ^{[1
]}

Petersen, Emily B. ^{[1
]}

Anderson, Hope D. ^{[2
]}

Hendrickson, Nathan R. ^{[1
]}

Compton, Jocelyn ^{[1
]}

Khorsand, Behnoush ^{[1
]}

Morris, Angie S. ^{[1
]}

Salem, Aliasger K. ^{[1
]}

Fredericks, Douglas C. ^{[1
]}

McKinley, Todd O. ^{[3
]}

Martin, James A. ^{[1
]}

机构：

[1] Univ Iowa, Iowa City, IA 52242 USA

[2] Wellesley Coll, Boston, MA 02481 USA

[3] Indiana Univ Hlth, Methodist Hosp, Orthopaed Trauma Serv, Indianapolis, IN 46202 USA

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2018年 / 10卷 / 427期

关键词：

TEMPERATURE-SENSITIVE HYDROGEL; ARTICULAR-CARTILAGE; CHONDROCYTE DEATH; MECHANICAL-STRESS; VITAMIN-E; METABOLISM; ARTHRITIS; OXYGEN; IMPACT; DEGENERATION;

D O I：

10.1126/scitranslmed.aan5372

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

We tested whether inhibiting mechanically responsive articular chondrocyte mitochondria after severe traumatic injury and preventing oxidative damage represent a viable paradigm for posttraumatic osteoarthritis (PTOA) prevention. We used a porcine hock intra-articular fracture (IAF) model well suited to human-like surgical techniques and with excellent anatomic similarities to human ankles. After IAF, amobarbital or N-acetylcysteine (NAC) was injected to inhibit chondrocyte electron transport or downstream oxidative stress, respectively. Effects were confirmed via spectrophotometric enzyme assays or glutathione/glutathione disulfide assays and immunohistochemical measures of oxidative stress. Amobarbital or NAC delivered after IAF provided substantial protection against PTOA at 6 months, including maintenance of proteoglycan content, decreased histological disease scores, and normalized chondrocyte metabolic function. These data support the therapeutic potential of targeting chondrocyte metabolism after injury and suggest a strong role for mitochondria in mediating PTOA.

引用

页数：14

共 55 条

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