Collagen XII Deficiency Increases the Risk of Anterior Cruciate Ligament Injury in Mice
Anterior cruciate ligament (ACL) rupture is a common knee injury for athletes. Although surgical reconstruction is recommended for the treatment of ACL ruptures, 100% functional recovery is unlikely. Therefore, the discovery of risk factors for ACL ruptures may prevent injury. Several studies have r...
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| Format: | Article |
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MDPI AG
2021-09-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/10/18/4051 |
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| author | Shin Fukusato Masashi Nagao Kei Fujihara Taiju Yoneda Kiyotaka Arai Manuel Koch Kazuo Kaneko Muneaki Ishijima Yayoi Izu |
| author_facet | Shin Fukusato Masashi Nagao Kei Fujihara Taiju Yoneda Kiyotaka Arai Manuel Koch Kazuo Kaneko Muneaki Ishijima Yayoi Izu |
| author_sort | Shin Fukusato |
| collection | DOAJ |
| description | Anterior cruciate ligament (ACL) rupture is a common knee injury for athletes. Although surgical reconstruction is recommended for the treatment of ACL ruptures, 100% functional recovery is unlikely. Therefore, the discovery of risk factors for ACL ruptures may prevent injury. Several studies have reported an association between polymorphisms of the collagen XII gene <i>COL12A1</i> and ACL rupture. Collagen XII is highly expressed in tendons and ligaments and regulates tissue structure and mechanical property. Therefore, we hypothesized that collagen XII deficiency may cause ACL injury. To elucidate the influence of collagen XII deficiency on ACL, we analyzed a mouse model deficient for <i>Col12a1</i>. Four- to 19-week-old male <i>Col12a1</i><sup>-/-</sup> and wild-type control mice were used for gait analysis; histological and immunofluorescent analysis of collagen XII, and real-time RT-PCR evaluation of <i>Col12a1</i> mRNA expression. The <i>Col12a1</i><sup>-/-</sup> mice showed an abnormal gait with an approximately 2.7-fold increase in step angle, suggesting altered step alignment. <i>Col12a1</i><sup>-/-</sup> mice displayed 20–60% ACL discontinuities, but 0% discontinuity in the posterior cruciate ligament. No discontinuities in knee ligaments were found in wild-type mice. Collagen XII mRNA expression in the ACL tended to decrease with aging. Our study demonstrates for the first time that collagen XII deficiency increases the risk of ACL injury. |
| first_indexed | 2024-03-10T07:34:15Z |
| format | Article |
| id | doaj.art-ceba4bc1159c4e6db79e4a802199a532 |
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| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T07:34:15Z |
| publishDate | 2021-09-01 |
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| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-ceba4bc1159c4e6db79e4a802199a5322023-11-22T13:38:43ZengMDPI AGJournal of Clinical Medicine2077-03832021-09-011018405110.3390/jcm10184051Collagen XII Deficiency Increases the Risk of Anterior Cruciate Ligament Injury in MiceShin Fukusato0Masashi Nagao1Kei Fujihara2Taiju Yoneda3Kiyotaka Arai4Manuel Koch5Kazuo Kaneko6Muneaki Ishijima7Yayoi Izu8Department of Medicine for Orthopaedics and Motor Organs, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, JapanDepartment of Medicine for Orthopaedics and Motor Organs, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, JapanDepartment of Laboratory Animal Science, Faculty of Veterinary Science, Okayama University of Science, 1-3 Ikoinooka, Imabari 794-8555, JapanDepartment of Laboratory Animal Science, Faculty of Veterinary Science, Okayama University of Science, 1-3 Ikoinooka, Imabari 794-8555, JapanDepartment of Veterinary Surgery, Faculty of Veterinary Science, Okayama University of Science, 1-1 Ridai-cho, Kita-ku, Okayama 700-0005, JapanInstitute for Dental Research and Oral Musculoskeletal Biology and Center for Biochemistry, Medical Faculty, University of Cologne, D-50931 Cologne, GermanyDepartment of Medicine for Orthopaedics and Motor Organs, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, JapanDepartment of Medicine for Orthopaedics and Motor Organs, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, JapanDepartment of Laboratory Animal Science, Faculty of Veterinary Science, Okayama University of Science, 1-3 Ikoinooka, Imabari 794-8555, JapanAnterior cruciate ligament (ACL) rupture is a common knee injury for athletes. Although surgical reconstruction is recommended for the treatment of ACL ruptures, 100% functional recovery is unlikely. Therefore, the discovery of risk factors for ACL ruptures may prevent injury. Several studies have reported an association between polymorphisms of the collagen XII gene <i>COL12A1</i> and ACL rupture. Collagen XII is highly expressed in tendons and ligaments and regulates tissue structure and mechanical property. Therefore, we hypothesized that collagen XII deficiency may cause ACL injury. To elucidate the influence of collagen XII deficiency on ACL, we analyzed a mouse model deficient for <i>Col12a1</i>. Four- to 19-week-old male <i>Col12a1</i><sup>-/-</sup> and wild-type control mice were used for gait analysis; histological and immunofluorescent analysis of collagen XII, and real-time RT-PCR evaluation of <i>Col12a1</i> mRNA expression. The <i>Col12a1</i><sup>-/-</sup> mice showed an abnormal gait with an approximately 2.7-fold increase in step angle, suggesting altered step alignment. <i>Col12a1</i><sup>-/-</sup> mice displayed 20–60% ACL discontinuities, but 0% discontinuity in the posterior cruciate ligament. No discontinuities in knee ligaments were found in wild-type mice. Collagen XII mRNA expression in the ACL tended to decrease with aging. Our study demonstrates for the first time that collagen XII deficiency increases the risk of ACL injury.https://www.mdpi.com/2077-0383/10/18/4051collagen XIIACL injuryrisk factor |
| spellingShingle | Shin Fukusato Masashi Nagao Kei Fujihara Taiju Yoneda Kiyotaka Arai Manuel Koch Kazuo Kaneko Muneaki Ishijima Yayoi Izu Collagen XII Deficiency Increases the Risk of Anterior Cruciate Ligament Injury in Mice Journal of Clinical Medicine collagen XII ACL injury risk factor |
| title | Collagen XII Deficiency Increases the Risk of Anterior Cruciate Ligament Injury in Mice |
| title_full | Collagen XII Deficiency Increases the Risk of Anterior Cruciate Ligament Injury in Mice |
| title_fullStr | Collagen XII Deficiency Increases the Risk of Anterior Cruciate Ligament Injury in Mice |
| title_full_unstemmed | Collagen XII Deficiency Increases the Risk of Anterior Cruciate Ligament Injury in Mice |
| title_short | Collagen XII Deficiency Increases the Risk of Anterior Cruciate Ligament Injury in Mice |
| title_sort | collagen xii deficiency increases the risk of anterior cruciate ligament injury in mice |
| topic | collagen XII ACL injury risk factor |
| url | https://www.mdpi.com/2077-0383/10/18/4051 |
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