scholarly journals Small RNA signatures of the anterior cruciate ligament from patients with knee joint osteoarthritis

Author(s):  
Yalda A. Kharaz ◽  
Yongxiang Fang ◽  
Tim Welting ◽  
Mandy Peffers ◽  
Eithne Comerford

The anterior cruciate ligaments are susceptible to degeneration, resulting in pain, reduced mobility and development of the degenerative joint disease osteoarthritis. There is currently a paucity of knowledge on how anterior cruciate ligament degeneration and disease can lead to osteoarthritis. Small non-coding RNAs (sncRNAs), such as microRNAs, and small nucleolar RNA, are important regulators of gene expression. We aimed to identify sncRNA profiles of human anterior cruciate ligaments to provide novel insights into their roles in osteoarthritis. RNA was extracted from the anterior cruciate ligaments of non-osteoarthritic knee joints (control) and end-stage osteoarthritis knee joints, used for small RNA sequencing and significantly differentially expressed sncRNAs defined. Bioinformatic analysis was undertaken on the differentially expressed miRNAs and their putative target mRNAs to investigate pathways and biological processes affected. Our analysis identified 184 sncRNA that were differentially expressed between control ACLs derived from osteoarthritic joints with a false discovery adjusted p value<0.05; 68 small nucleolar RNAs, 26 small nuclear RNAs and 90 microRNAs. We identified both novel and previously identified (miR-206, -101, -365 and -29b and -29c) osteoarthritis-related microRNAs and other sncRNAs (including SNORD74, SNORD114, SNORD72) differentially expressed in ligaments derived from osteoarthritic joints. Significant cellular functions deduced by the differentially expressed miRNAs included differentiation of muscle (P<0.001), inflammation (P<1.42E−10), proliferation of chondrocytes (P<0.03), fibrosis (P<0.001) and cell viability (P<0.03). Putative mRNAs were associated with the canonical pathways Hepatic Fibrosis Signalling (P<3.7E-32), and Osteoarthritis (P<2.2E−23). Biological processes included apoptosis (P<1.7E−85), fibrosis (P<1.2E−79), inflammation (P<3.4E−88), necrosis (P<7.2E−88) and angiogenesis (P<5.7E−101). SncRNAs are important regulators of anterior cruciate disease during osteoarthritis and may be used as therapeutic targets to prevent and manage anterior cruciate ligament disease and the resultant osteoarthritis.

2003 ◽  
Vol 31 (2) ◽  
pp. 164-167 ◽  
Author(s):  
Mandi J. Lopez ◽  
Mark D. Markel

Background: The use of radiofrequency energy to treat damaged anterior cruciate ligaments is gaining popularity. However, complete rupture of the ligament after treatment has been reported. Purpose: To evaluate the effect of thermal energy applied arthroscopically to normal, intact anterior cruciate ligaments in mature dogs. Study Design: Controlled laboratory study. Methods: Monopolar radiofrequency energy was applied to the normal anterior cruciate ligament of 1 knee in 18 dogs. The contralateral anterior cruciate ligament (also normal) was sham treated. Force-plate gait analysis was performed preoperatively and at 4, 8, 12, 16, 26, and 36 weeks after surgery. Anterior cruciate ligament rupture was detected by a sudden onset of nonweightbearing and a positive drawer sign. Results: All treated ligaments ruptured approximately 55 days after surgery (mean, 55 days; standard error, 1.6). Conclusions: Although monopolar radiofrequency energy may have some potential in the treatment of lax anterior cruciate ligaments, in the application described here the result was a highly predictable deterioration and rupture of all treated anterior cruciate ligaments. Clinical Relevance: On the basis of these findings, we strongly recommend that strict selection and application criteria be used when considering use of this modality on anterior cruciate ligaments that are stretched or partially disrupted, or both. Use of this modality should be followed by adherence to a highly conservative rehabilitation protocol.


2019 ◽  
Vol 33 (07) ◽  
pp. 655-658
Author(s):  
Takafumi Hiranaka ◽  
Yuichi Hida ◽  
Takaaki Fujishiro ◽  
Tomoyuki Kamenaga ◽  
Kenichi Kikuchi ◽  
...  

AbstractThe anterior cruciate ligament (ACL) plays an important role in knee kinematics. Unicompartmental knee arthroplasty (UKA) preserves the ACL, an advantage over total knee arthroplasty (TKA), where it is sacrificed. This study aims to evaluate how often functional ACLs are sacrificed in arthroplasty. The type of arthroplasty (TKA or UKA) and condition of the ACL were studied in a total of 1,586 knees in 1,052 patients who underwent knee arthroplasties. Of 1,586 knees, TKA was performed on 653 knees (41%) and UKA on 933 knees (59%). The ACL was functioning in 77% of all knees. Of the TKA knees, the ACL was functioning in 357 knees (55%). Of these, around 30% of the functioning ACLs were sacrificed to perform TKA. To improve postoperative patient satisfaction after knee arthroplasty, further study regarding relationship between ACL preservation and clinical outcome will be required.


2009 ◽  
Vol 37 (7) ◽  
pp. 1282-1287 ◽  
Author(s):  
Ajit M.W. Chaudhari ◽  
Eric A. Zelman ◽  
David C. Flanigan ◽  
Christopher C. Kaeding ◽  
Haikady N. Nagaraja

1980 ◽  
Vol 102 (3) ◽  
pp. 190-193 ◽  
Author(s):  
J.-M. Dorlot ◽  
M. Ait Ba Sidi ◽  
G. M. Tremblay ◽  
G. Drouin

This paper describes the results of an investigation on the mechanical properties of canine anterior cruciate ligaments. A total of 38 ligaments were tested. It is shown that the completely reversible (elastic) range of strain is limited to 14 percent elongation, corresponding to an applied load of 200 N. Within this range each specimen was tested at different strain rates varying from 0.12 percent/s to 220 percent/s and it is demonstrated that the mechanical behavior of the ligaments is not sensitive to strain rate in the range investigated. After completion of tests in the reversible range, of strain ten ligaments were frozen and similar tests were performed after thawing. It is shown that freezing produces alterations of the mechanical properties. The ligaments become more rigid than when they are tested in fresh conditions. From room temperature up to 45C, the load-elongation relationship is not significantly dependent upon test temperature.


2005 ◽  
Vol 33 (8) ◽  
pp. 1166-1173 ◽  
Author(s):  
Keishi Marumo ◽  
Mitsuru Saito ◽  
Tsuneo Yamagishi ◽  
Katsuyuki Fujii

Background There is little information documenting whether the phenomenon of “ligamentization,” as proposed by Amiel, occurs in the human anterior cruciate ligament after clinically effective reconstruction. To clarify this point, we analyzed biochemical differences between the native anterior cruciate ligament; the patellar, semitendinosus, and gracilis tendons; and anterior cruciate ligaments reconstructed with autografts. Study Design Cohort study; Level of evidence, 2. Methods Fifty patients who underwent arthroscopically assisted anterior cruciate ligament reconstruction using either semi-tendinosus and gracilis tendon or bone-patellar tendon-bone autografts were selected for the study. Samples of grafted tissue were collected during arthroscopy and quantitatively analyzed for collagen content and the amount of reducible and nonreducible crosslinks at 4 to 6 postoperative months in patients with semitendinosus and gracilis tendon grafts and at 11 to 13 months in all patients with semitendinosus and gracilis tendon or bone-patellar tendon-bone grafts. Results The total collagen content and nonreducible/reducible crosslink ratios increased significantly during the postoperative period (P < .05). The dihydroxylysinonorleucine/hydroxylysinonorleucine ratio was 3.11 ± 0.56 in the native anterior cruciate ligament, 1.21 ± 0.47 in the patellar tendon, and 3.59 ± 1.58 in the anterior cruciate ligaments reconstructed with bone-patellar tendon-bone autografts 1 year after surgery. The dihydroxylysinonorleucine/hydroxylysinonorleucine ratio in both semitendinosus and gracilis tendons was less than 1.0. However, in anterior cruciate ligaments reconstructed with semitendinosus and gracilis tendon autografts, it was 2.34 ± 0.98 at 4 to 6 months and 3.43 ± 1.61 at 11 to 13 months after the operation. Conclusions After anterior cruciate ligament reconstruction with autografts, biochemical characteristics of the graft resembled those of the native anterior cruciate ligament. These findings suggest that, regarding the amount of collagen crosslinks and their architecture, the phenomenon of ligamentization occurs in the successfully reconstructed human anterior cruciate ligament within 1 year after operation.


PeerJ ◽  
2022 ◽  
Vol 10 ◽  
pp. e12781
Author(s):  
Huining Gu ◽  
Siyuan Chen ◽  
Mingzheng Zhang ◽  
Yu Wen ◽  
Bin Li

Long noncoding RNAs (lncRNAs), as a novel regulatory factor, are considered to play a vital role in various biological processes and diseases. However, the overall expression profile and biological functions of lncRNAs in the partially injured anterior cruciate ligament (ACL) and medial collateral ligament (MCL) have not been clearly explored. Partially injured models of ACL and MCL were established in 3-month-old healthy male New Zealand white rabbits. Expression of lncRNAs and mRNAs in the ligament tissue was detected by high-throughput sequencing technology, and biological functions of differentially expressed RNAs were evaluated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Validation of several differentially expressed RNAs was performed using quantitative real-time PCR (qRT-PCR). Protein-protein interaction (PPI) analysis and competitive endogenous RNA (ceRNA) prediction were used to identify interactions among hub genes and the interaction among lncRNAs, miRNAs, and mRNAs. The results showed that compared with the normal group, there were 267 mRNAs and 329 lncRNAs differentially expressed in ACL and 726 mRNAs and 609 lncRNAs in MCL in the injured group. Compared with MCL, 420 mRNAs and 470 lncRNAs were differentially expressed in ACL in the normal group; 162 mRNAs and 205 lncRNAs were differentially expressed in ACL in the injured group. Several important lncRNAs and genes were identified, namely, COL7A1, LIF, FGFR2, EPHA2, CSF1, MMP2, MMP9, SOX5, LOX, MSTRG.1737.1, MSTRG.26038.25, MSTRG.20209.5, MSTRG.22764.1, and MSTRG.18113.1, which are closely related to inflammatory response, tissue damage repair, cell proliferation, differentiation, migration, and apoptosis. Further study of the functions of these genes may help to better understand the specific molecular mechanisms underlying the occurrence of endogenous repair disorders in ACL, which may provide new ideas for further exploration of effective means to promote endogenous repair of ACL injury.


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