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Article ; Online: Bridge-Enhanced Anterior Cruciate Ligament Repair Leads to Greater Limb Asymmetry and Less Cartilage Damage Than Untreated ACL Transection or ACL Reconstruction in the Porcine Model.

Karamchedu, Naga Padmini / Murray, Martha M / Sieker, Jakob T / Proffen, Benedikt L / Portilla, Gabriela / Costa, Meggin Q / Molino, Janine / Fleming, Braden C

The American journal of sports medicine

2021 Volume 49, Issue 3, Page(s) 667–674

Abstract: Background: The extent of posttraumatic osteoarthritis (PTOA) in the porcine anterior cruciate ligament (ACL) transection model is dependent on the surgical treatment selected. In a previous study, animals treated with bridge-enhanced ACL repair using a ...

Abstract	Background: The extent of posttraumatic osteoarthritis (PTOA) in the porcine anterior cruciate ligament (ACL) transection model is dependent on the surgical treatment selected. In a previous study, animals treated with bridge-enhanced ACL repair using a tissue-engineered implant developed less PTOA than those treated with ACL reconstruction (ACLR). Alterations in gait, including asymmetric weightbearing and shorter stance times, have been noted in clinical studies of subjects with osteoarthritis. Hypothesis: Animals receiving a surgical treatment that results in less PTOA (ie, bridge-enhanced ACL repair) would exhibit fewer longitudinal postoperative gait asymmetries over a 1-year period when compared with treatments that result in greater PTOA (ie, ACLR and ACL transection). Study design: Controlled laboratory study. Methods: Thirty-six Yucatan minipigs underwent ACL transection and were randomized to receive (1) no further treatment, (2) ACLR, or (3) bridge-enhanced ACL repair. Gait analyses were performed preoperatively, and at 4, 12, 26, and 52 weeks postoperatively. Macroscopic cartilage assessments were performed at 52 weeks. Results: Knees treated with bridge-enhanced ACL repair had less macroscopic damage in the medial tibial plateau than those treated with ACLR or ACL transection (adjusted Conclusion: Contrary to our hypothesis, the surgical treatment resulting in less macroscopic cartilage damage (ie, bridge-enhanced ACL repair) exhibited greater asymmetry in load-related gait parameters than the other surgical groups. This finding suggests that increased offloading of the surgical knee may be associated with a slower rate of PTOA development. Clinical relevance: Less cartilage damage at 52 weeks was found in the surgical group that continued to protect the limb from full body weight during gait. This finding suggests that protection of the knee from maximum stresses may be important in minimizing the development of PTOA in the ACL-injured knee within 1 year.
MeSH term(s)	Animals ; Anterior Cruciate Ligament/surgery ; Anterior Cruciate Ligament Injuries/surgery ; Anterior Cruciate Ligament Reconstruction ; Biomechanical Phenomena ; Knee Joint/surgery ; Swine ; Swine, Miniature
Language	English
Publishing date	2021-02-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	197482-8
ISSN	1552-3365 ; 0363-5465
ISSN (online)	1552-3365
ISSN	0363-5465
DOI	10.1177/0363546521989265
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Article ; Online: Peripheral shift in the viable chondrocyte population of the medial femoral condyle after anterior cruciate ligament injury in the porcine knee.

Costa, Meggin Q / Murray, Martha M / Sieker, Jakob T / Karamchedu, Naga Padmini / Proffen, Benedikt L / Fleming, Braden C

PloS one

2021 Volume 16, Issue 8, Page(s) e0256765

Abstract: Anterior cruciate ligament injuries result in posttraumatic osteoarthritis in the medial compartment of the knee, even after surgical treatment. How the chondrocyte distribution within the articular cartilage changes early in this process is currently ... ...

Abstract	Anterior cruciate ligament injuries result in posttraumatic osteoarthritis in the medial compartment of the knee, even after surgical treatment. How the chondrocyte distribution within the articular cartilage changes early in this process is currently unknown. The study objective was to investigate the chondrocyte distribution within the medial femoral condyle after an anterior cruciate ligament transection in a preclinical model. Forty-two adolescent Yucatan minipigs were allocated to receive unilateral anterior cruciate ligament surgery (n = 36) or no surgery (n = 6). Central coronal sections of the medial femoral condyle were obtained at 1- and 4 weeks after surgery, and the chondrocyte distribution was measured via whole slide imaging and a cell counting batch processing tool utilized in ImageJ. Ki-67 immunohistochemistry was performed to identify proliferating cells. Empty lacunae, karyolysis, karyorrhexis, and pyknosis were used to identify areas of irreversible cell injury. The mean area of irreversible cell injury was 0% in the intact controls, 13.4% (95% confidence interval: 6.4, 20.3) at 1-week post-injury and 19.3% (9.7, 28.9) at 4 weeks post-injury (p < .015). These areas occurred closest to the femoral intra-articular notch. The remaining areas containing viable chondrocytes had Ki-67-positive cells (p < .02) and increased cell density in the middle (p < .03) and deep zones (p = .001). For the entire section, the total chondrocyte number did not change significantly post-operatively; however, the density of cells in the peripheral regions of the medial femoral condyle increased significantly at 1- and 4 weeks post-injury relative to the intact control groups (p = .032 and .004, respectively). These data demonstrate a peripheral shift in the viable chondrocyte population of the medial femoral condyle after anterior cruciate ligament injury and further suggest that chondrocytes with the capacity to proliferate are not confined to one particular cartilage layer.
MeSH term(s)	Animals ; Anterior Cruciate Ligament Injuries/pathology ; Cell Count ; Cell Survival ; Chondrocytes/pathology ; Femur/pathology ; Ki-67 Antigen/metabolism ; Knee Joint/pathology ; Swine
Chemical Substances	Ki-67 Antigen
Language	English
Publishing date	2021-08-26
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0256765
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Article: Biomaterialien in der Sportmedizin - Anwendungen bei Knorpel-, Knochen-, und Bandverletzungen

Proffen, Benedikt L. / Sieker, Jakob T.

Sport-Orthopädie, Sport-Traumatologie

2014 Volume 30, Issue 3, Page(s) 220

Language	German
Document type	Article
ZDB-ID	1233784-5
ISSN	0177-0438 ; 0949-328X
Database	Current Contents Medicine

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Article ; Online: Peripheral shift in the viable chondrocyte population of the medial femoral condyle after anterior cruciate ligament injury in the porcine knee.

Meggin Q Costa / Martha M Murray / Jakob T Sieker / Naga Padmini Karamchedu / Benedikt L Proffen / Braden C Fleming

PLoS ONE, Vol 16, Iss 8, p e

2021 Volume 0256765

Abstract	Anterior cruciate ligament injuries result in posttraumatic osteoarthritis in the medial compartment of the knee, even after surgical treatment. How the chondrocyte distribution within the articular cartilage changes early in this process is currently unknown. The study objective was to investigate the chondrocyte distribution within the medial femoral condyle after an anterior cruciate ligament transection in a preclinical model. Forty-two adolescent Yucatan minipigs were allocated to receive unilateral anterior cruciate ligament surgery (n = 36) or no surgery (n = 6). Central coronal sections of the medial femoral condyle were obtained at 1- and 4 weeks after surgery, and the chondrocyte distribution was measured via whole slide imaging and a cell counting batch processing tool utilized in ImageJ. Ki-67 immunohistochemistry was performed to identify proliferating cells. Empty lacunae, karyolysis, karyorrhexis, and pyknosis were used to identify areas of irreversible cell injury. The mean area of irreversible cell injury was 0% in the intact controls, 13.4% (95% confidence interval: 6.4, 20.3) at 1-week post-injury and 19.3% (9.7, 28.9) at 4 weeks post-injury (p < .015). These areas occurred closest to the femoral intra-articular notch. The remaining areas containing viable chondrocytes had Ki-67-positive cells (p < .02) and increased cell density in the middle (p < .03) and deep zones (p = .001). For the entire section, the total chondrocyte number did not change significantly post-operatively; however, the density of cells in the peripheral regions of the medial femoral condyle increased significantly at 1- and 4 weeks post-injury relative to the intact control groups (p = .032 and .004, respectively). These data demonstrate a peripheral shift in the viable chondrocyte population of the medial femoral condyle after anterior cruciate ligament injury and further suggest that chondrocytes with the capacity to proliferate are not confined to one particular cartilage layer.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
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Article ; Online: Bio-enhanced repair of the anterior cruciate ligament.

Proffen, Benedikt L / Sieker, Jakob T / Murray, Martha M

Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association

2015 Volume 31, Issue 5, Page(s) 990–997

Abstract: Suture repair of the anterior cruciate ligament (ACL) has been widely abandoned in favor of ACL reconstruction, largely because of the high rates of failure and unreliability of the outcomes after suture repair. However, there have been recent basic ... ...

Abstract	Suture repair of the anterior cruciate ligament (ACL) has been widely abandoned in favor of ACL reconstruction, largely because of the high rates of failure and unreliability of the outcomes after suture repair. However, there have been recent basic science studies that suggest that combining a suture repair with a biological adjunct may improve the results of suture repair of the ACL, with several studies in large animal models showing equivalent strength of an ACL treated with bio-enhanced repaired to that of an ACL graft at 3, 6, and 12 months after surgery. In addition, the groups treated with bio-enhanced repair had significantly less osteoarthritis when compared with the animals undergoing ACL reconstruction. These findings have led to a renewed interest in bio-enhanced primary repair as a way to make repair of the ACL a viable option for a select group of patients in the future.
MeSH term(s)	Animals ; Anterior Cruciate Ligament/physiology ; Anterior Cruciate Ligament/surgery ; Collagen/therapeutic use ; Humans ; Intercellular Signaling Peptides and Proteins/therapeutic use ; Platelet-Rich Plasma ; Regeneration ; Regenerative Medicine ; Tissue Engineering/methods ; Tissue Scaffolds
Chemical Substances	Intercellular Signaling Peptides and Proteins ; Collagen (9007-34-5)
Language	English
Publishing date	2015-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	632528-2
ISSN	1526-3231 ; 0749-8063
ISSN (online)	1526-3231
ISSN	0749-8063
DOI	10.1016/j.arthro.2014.11.016
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Article ; Online: Proteolysis and cartilage development are activated in the synovium after surgical induction of post traumatic osteoarthritis.

Ayturk, Ugur M / Sieker, Jakob T / Haslauer, Carla M / Proffen, Benedikt L / Weissenberger, Manuela H / Warman, Matthew L / Fleming, Braden C / Murray, Martha M

PloS one

2020 Volume 15, Issue 2, Page(s) e0229449

Abstract: Anterior cruciate ligament (ACL) transection surgery in the minipig induces post-traumatic osteoarthritis (PTOA) in a pattern similar to that seen in human patients after ACL injury. Prior studies have reported the presence of cartilage matrix-degrading ... ...

Abstract	Anterior cruciate ligament (ACL) transection surgery in the minipig induces post-traumatic osteoarthritis (PTOA) in a pattern similar to that seen in human patients after ACL injury. Prior studies have reported the presence of cartilage matrix-degrading proteases, such as Matrix metalloproteinase-1 (MMP-1) and A disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4), in the synovial fluid of injured or arthritic joints; however, the tissue origin of these proteases is unknown. The objective of this study was to identify transcriptional processes activated in the synovium after surgical induction of PTOA with ACL transection, and to determine if processes associated with proteolysis were enriched in the synovium after ACL transection. Unilateral ACL transection was performed in adolescent Yucatan minipigs and synovium samples were collected at 1, 5, 9, and 14 days post-injury. Transcriptome-wide gene expression levels were determined using bulk RNA-Sequencing in the surgical animals and control animals with healthy knees. The greatest number of transcripts with significant changes was observed 1 day after injury. These changes were primarily associated with cellular proliferation, consistent with measurements of increased cellularity of the synovium at the two-week time point. At five to 14 days, the expression of transcripts relating to proteolysis and cartilage development was significantly enriched. While protease inhibitor-encoding transcripts (TIMP2, TIMP3) represented the largest fraction of protease-associated transcripts in the uninjured synovium, protease-encoding transcripts (including MMP1, MMP2, ADAMTS4) predominated after surgery. Cartilage development-associated transcripts that are typically not expressed by synovial cells, such as ACAN and COMP, were enriched in the synovium following ACL-transection. The upregulation in both catabolic processes (proteolysis) and anabolic processes (cartilage development) suggests that the synovium plays a complex, balancing role in the early response to PTOA induction.
MeSH term(s)	Animals ; Biomarkers/metabolism ; Cartilage, Articular/metabolism ; Cartilage, Articular/pathology ; Chondrogenesis/genetics ; Male ; Osteoarthritis/genetics ; Osteoarthritis/pathology ; Osteoarthritis/surgery ; Proteolysis ; Swine ; Swine, Miniature ; Synovial Membrane/metabolism ; Synovial Membrane/pathology ; Transcriptome
Chemical Substances	Biomarkers
Language	English
Publishing date	2020-02-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0229449
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Article: Symptomatic loosening of a total knee arthroplasty caused by a tibial chondrosarcoma - a case report.

Sieker, Jakob T / Rudert, Maximilian / Steinert, Andre F

SpringerPlus

2014 Volume 3, Page(s) 308

Abstract: Premature implant loosening following total knee arthroplasty (TKA) can have several causes. In this article we report on a rare case of a 74 year old male patient suffering tibial component loosening 14 month after primary TKA. The patient did neither ... ...

Abstract	Premature implant loosening following total knee arthroplasty (TKA) can have several causes. In this article we report on a rare case of a 74 year old male patient suffering tibial component loosening 14 month after primary TKA. The patient did neither have any malignancies nor joint arthroplasty before. Upon clinical examination the range of motion in the diseased knee was painfully restricted to 80° of knee flexion, with the patient increasingly suffering sleeping and resting pain, and also at weight bearing. In standard radiographs, loosening of the TKA due to a large osteolysis at the tibial component was evident. Local computed tomography (CT) of the right knee revealed loosening of the tibial component due to a presumably malign bone tumor. For determination of the final diagnosis a representative biopsy of the tumor was taken by open surgery prior to the tumor resection. Histopathologic evaluation of the biopsy revealed a periprosthetic myxoid chondrosarcoma of the proximal tibia. Pre-operative staging examination included CT scans of lung and abdomen, as well as a bone scintigraphy which revealed no signs of tumor metastasis in the body. Surgical management comprised wide tumor resection and implantation of a hinged tumor knee arthroplasty with replacements of the distal femur and proximal tibia, as well as a patella tendon replacement using a synthetic ligament. Revision surgery was necessary twice due to impaired wound healing and critical soft tissue coverage, and treatment included a gastrocnemius muscle flap with skin mesh graft covering. Unfortunately long-term follow-up examinations could not be obtained, as the patient deceased due to an alveolitis during rehabilitation. In summary, the specifics of this rare case of aseptic TKA loosening, and the unusual circumstances of chondrosarcoma diagnosis and treatment are informative for those providing surgical treatment of similar cases.
Language	English
Publishing date	2014-06-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661116-8
ISSN	2193-1801
ISSN	2193-1801
DOI	10.1186/2193-1801-3-308
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Article: Analytic Sensitivity of 3 Nucleic Acid Detection Assays in Diagnosis of SARS-CoV-2 Infection.

Sieker, Jakob T / Horowitz, Coby / Hu, Cheng-Tsung K / Lacombe-Daphnis, Meriane / Chirokas, Bernadette / Pina, Coteia / Heger, Nicholas E / Rabson, Arthur R / Zhou, Ming / Bogen, Steven A / Horowitz, Gary L

The journal of applied laboratory medicine

2021 Volume 6, Issue 2, Page(s) 421–428

Abstract: Background: Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcription PCR is the primary method to diagnose coronavirus disease 2019 (COVID-19). However, the analytic sensitivity required is not well defined and ... ...

Abstract	Background: Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcription PCR is the primary method to diagnose coronavirus disease 2019 (COVID-19). However, the analytic sensitivity required is not well defined and it is unclear how available assays compare. Methods: For the Abbott RealTime SARS-CoV-2 assay (m2000; Abbott Molecular), we determined that it could detect viral concentrations as low as 26 copies/mL, we defined the relationship between cycle number and viral concentrations, and we tested naso- and oropharyngeal swab specimens from 8538 consecutive individuals. Using the m2000 as a reference assay method, we described the distribution of viral concentrations in these patients. We then used selected clinical specimens to determine the positive percent agreement of 2 other assays with more rapid turnaround times [Cepheid Xpert Xpress (GeneXpert; Cepheid); n = 27] and a laboratory developed test on the Luminex ARIES system [ARIES LDT (Luminex); n = 50] as a function of virus concentrations, from which we projected their false-negative rates in our patient population. Results: SARS-CoV-2 was detected in 27% (95% CI: 26%-28%) of all specimens. Estimated viral concentrations were widely distributed, and 17% (95% CI: 16%-19%) of positive individuals had viral concentrations <845 copies/mL. Positive percent agreement was strongly related to viral concentration, and reliable detection (i.e., ≥95%) was observed at concentrations >100 copies/mL for the GeneXpert but not the ARIES LDT, corresponding to projected false-negative rates of 4% (95% CI: 0%-21%) and 27% (95% CI: 11%-46%), respectively. Conclusions: Substantial proportions of clinical specimens have low to moderate viral concentrations and may be missed by methods with less analytic sensitivity.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; COVID-19/diagnosis ; COVID-19/virology ; COVID-19 Nucleic Acid Testing/instrumentation ; False Negative Reactions ; Female ; Humans ; Limit of Detection ; Male ; Middle Aged ; RNA, Viral/isolation & purification ; Reagent Kits, Diagnostic ; Real-Time Polymerase Chain Reaction/instrumentation ; Reproducibility of Results ; Retrospective Studies ; SARS-CoV-2/genetics ; SARS-CoV-2/isolation & purification
Chemical Substances	RNA, Viral ; Reagent Kits, Diagnostic
Language	English
Publishing date	2021-03-05
Publishing country	England
Document type	Journal Article
ISSN	2576-9456
ISSN	2576-9456
DOI	10.1093/jalm/jfaa187
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Article ; Online: Synovial fluid proteome changes in ACL injury-induced posttraumatic osteoarthritis: Proteomics analysis of porcine knee synovial fluid.

Kiapour, Ata M / Sieker, Jakob T / Proffen, Benedikt L / Lam, TuKiet T / Fleming, Braden C / Murray, Martha M

PloS one

2019 Volume 14, Issue 3, Page(s) e0212662

Abstract: Surgical transection of the anterior cruciate ligament (ACL) in the porcine model leads to posttraumatic osteoarthritis if left untreated. However, a recently developed surgical treatment, bridge-enhanced ACL repair, prevents further cartilage damage. ... ...

Abstract	Surgical transection of the anterior cruciate ligament (ACL) in the porcine model leads to posttraumatic osteoarthritis if left untreated. However, a recently developed surgical treatment, bridge-enhanced ACL repair, prevents further cartilage damage. Since the synovial fluid bathes all the intrinsic structures of knee, we reasoned that a comparative analysis of synovial fluid protein contents could help to better understand the observed chondroprotective effects of the bridge-enhanced ACL repair. We hypothesized that post-surgical changes in the synovial fluid proteome would be different in the untreated and repaired knees, and those changes would correlate with the degree of cartilage damage. Thirty adolescent Yucatan mini-pigs underwent unilateral ACL transection and were randomly assigned to either no further treatment (ACLT, n = 14) or bridge-enhanced ACL repair (BEAR, n = 16). We used an isotopically labeled high resolution LC MS/MS-based proteomics approach to analyze the protein profile of synovial fluid at 6 and 12 months after ACL transection in untreated and repaired porcine knees. A linear mixed effect model was used to compare the normalized protein abundance levels between the groups at each time point. Bivariate linear regression analyses were used to assess the correlations between the macroscopic cartilage damage (total lesion area) and normalized abundance levels of each of the identified secreted proteins. There were no significant differences in cartilage lesion area or quantitative abundance levels of the secreted proteins between the ACLT and BEAR groups at 6 months. However, by 12 months, greater cartilage damage was seen in the ACLT group compared to the BEAR group (p = 0.005). This damage was accompanied by differences in the abundance levels of secreted proteins, with higher levels of Vitamin K-dependent protein C (p = 0.001), and lower levels of Apolipoprotein A4 (p = 0.021) and Cartilage intermediate layer protein 1 (p = 0.049) in the ACLT group compared to the BEAR group. There were also group differences in the secreted proteins that significantly changed in abundance between 6 and 12 months in ACLT and BEAR knees. Increased concentration of Ig lambda-1 chain C regions and decreased concentration of Hemopexin, Clusterin, Coagulation factor 12 and Cartilage intermediate layer protein 1 were associated with greater cartilage lesion area. In general, ACLT knees had higher concentrations of pro-inflammatory proteins and lower concentrations of anti-inflammatory proteins than BEAR group. In addition, the ACLT group had a lower and declining synovial concentrations of CILP, in contrast to a consistently high abundance of CILP in repaired knees. These differences suggest that the knees treated with bridge-enhanced ACL repair may be maintaining an environment that is more protective of the extracellular matrix, a function which is not seen in the ACLT knees.
MeSH term(s)	Animals ; Cartilage, Articular/metabolism ; Cartilage, Articular/pathology ; Knee Injuries/complications ; Knee Injuries/metabolism ; Knee Injuries/pathology ; Knee Joint/metabolism ; Knee Joint/pathology ; Osteoarthritis, Knee/etiology ; Osteoarthritis, Knee/metabolism ; Osteoarthritis, Knee/pathology ; Proteome/metabolism ; Swine ; Swine, Miniature ; Synovial Membrane/metabolism ; Synovial Membrane/pathology
Chemical Substances	Proteome
Language	English
Publishing date	2019-03-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0212662
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Article ; Online: Synovial fluid proteome changes in ACL injury-induced posttraumatic osteoarthritis

Ata M Kiapour / Jakob T Sieker / Benedikt L Proffen / TuKiet T Lam / Braden C Fleming / Martha M Murray

PLoS ONE, Vol 14, Iss 3, p e

Proteomics analysis of porcine knee synovial fluid.

2019 Volume 0212662

Abstract	Surgical transection of the anterior cruciate ligament (ACL) in the porcine model leads to posttraumatic osteoarthritis if left untreated. However, a recently developed surgical treatment, bridge-enhanced ACL repair, prevents further cartilage damage. Since the synovial fluid bathes all the intrinsic structures of knee, we reasoned that a comparative analysis of synovial fluid protein contents could help to better understand the observed chondroprotective effects of the bridge-enhanced ACL repair. We hypothesized that post-surgical changes in the synovial fluid proteome would be different in the untreated and repaired knees, and those changes would correlate with the degree of cartilage damage. Thirty adolescent Yucatan mini-pigs underwent unilateral ACL transection and were randomly assigned to either no further treatment (ACLT, n = 14) or bridge-enhanced ACL repair (BEAR, n = 16). We used an isotopically labeled high resolution LC MS/MS-based proteomics approach to analyze the protein profile of synovial fluid at 6 and 12 months after ACL transection in untreated and repaired porcine knees. A linear mixed effect model was used to compare the normalized protein abundance levels between the groups at each time point. Bivariate linear regression analyses were used to assess the correlations between the macroscopic cartilage damage (total lesion area) and normalized abundance levels of each of the identified secreted proteins. There were no significant differences in cartilage lesion area or quantitative abundance levels of the secreted proteins between the ACLT and BEAR groups at 6 months. However, by 12 months, greater cartilage damage was seen in the ACLT group compared to the BEAR group (p = 0.005). This damage was accompanied by differences in the abundance levels of secreted proteins, with higher levels of Vitamin K-dependent protein C (p = 0.001), and lower levels of Apolipoprotein A4 (p = 0.021) and Cartilage intermediate layer protein 1 (p = 0.049) in the ACLT group compared to the BEAR group. There were also group differences in the secreted proteins that significantly changed in abundance between 6 and 12 months in ACLT and BEAR knees. Increased concentration of Ig lambda-1 chain C regions and decreased concentration of Hemopexin, Clusterin, Coagulation factor 12 and Cartilage intermediate layer protein 1 were associated with greater cartilage lesion area. In general, ACLT knees had higher concentrations of pro-inflammatory proteins and lower concentrations of anti-inflammatory proteins than BEAR group. In addition, the ACLT group had a lower and declining synovial concentrations of CILP, in contrast to a consistently high abundance of CILP in repaired knees. These differences suggest that the knees treated with bridge-enhanced ACL repair may be maintaining an environment that is more protective of the extracellular matrix, a function which is not seen in the ACLT knees.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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