연구논문

세부과제번호 2014M3A9D5A01073658 단계 1단계 2차년도
세부과제명 골격계 질환 분석 공동 유/무 N
SCI여부 N 게재년월 2015-11
논문제목 A novel method to detect articular chondrocyte death during early stages of osteoarthritis using a non-invasive ApoPep-1 probe.
총저자명 Xiangguo Che†, Lianhua Chi†, Clara Yongjoo Park, Gyoung-Ho Cho, Narae Park, Seong-Gon Kim, Byung-Heon Lee and Je-Yong Choi
학술지명 Arthritis Res Ther 게재권(호) 17
저널구분 - 페이지수 309-319
참여연구원 - 연구책임자 최제용
과제기여도 25 PMID -
사사기관수 - IF (년도) 3.753
제1저자 Xiangguo Che 교신저자 Je-Yong Choi
공동저자 -
초록
Introduction Current methods for early diagnosis of osteoarthritis (OA) are limited. We assessed whether in vivo detection of chondrocyte death by ApoPep-1 (CQRPPR), a peptide that binds to histone H1 of apoptotic and necrotic cells, could be used to detect the initiation of OA. Methods Apoptosis-induced ATDC5 cells were labeled with Annexin V and ApoPep-1. Surgical destabilization of the medial meniscus (DMM) was performed on both knees of 12-week-old male mice and severity of OA was determined by histological analysis according to the Osteoarthritis Research Society International (OARSI) guidelines. At 1, 2, 4, and 8 weeks post-surgery, mice were intravenously injected with fluorescence-labeled ApoPep-1 or control peptide and in vivo imaging was performed within 30 minutes of injection by near-infrared fluorescence (NIRF). Binding of ApoPep-1 to OA joints was demonstrated by ex vivo imaging and immunofluorescent staining using TUNEL and histone H1 and type II collagen antibodies. Results Strong signals of ApoPep-1 were observed on the apoptotic ATDC5 cells. Knees corresponded to grade II, III, and V OA at 2, 4, and 8 weeks after DMM, respectively. Between 2 and 8 weeks after surgery, the in vivo NIRF signal at OA-ApoPep1-injected joints was consistently stronger than sham-operated or OA-control peptide-injected joints. ApoPep-1, TUNEL, and histone H1 signals were stronger in grade II OA cartilage than sham-operated cartilage when detected by immunofluorescent staining. Type II collagen expression was similar between grade II OA and sham group. Conclusion ApoPep-1 can be used to detect OA in vivo by binding to apoptotic chondrocytes. This is a novel, sensitive, and rapid method which can detect apoptotic cells in OA rodent models soon after its onset. Keywords Early diagnosis of osteoarthritis Articular chondrocyte Apoptosis ApoPep-1
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