Long-term Results of Partial Release Versus Nonrelease of the Posterior Cruciate Ligament at Cruciate-Retaining Total Knee Arthroplasty: Minimum 15-Year Follow-up.

The goal of this study was to compare the clinical and radiologic results of posterior cruciate ligament (PCL) partial release and PCL nonrelease in performing cruciate-retaining total knee arthroplasty (CR-TKA) for a long-term follow-up period of greater than 15 years. A total of 224 patients underwent CR-TKA in our hospital from June 1996 to April 2002 with greater than 15 years of follow-up. We divided the subjects into 2 groups based on release of the PCL. Group 1 was the PCL partial release group (88 cases), and group 2 was the PCL nonrelease group (136 cases). The mean follow-up period was 16.8 years (range, 15.5-19.5 years). We compared the clinical results by measuring the Knee Society Score (KSS), Hospital for Special Surgery (HSS) score, and Western Ontario and McMaster Universities Osteoarthritis (WOMAC) score preoperatively and at the last follow-up. For radiologic results, the Knee Society Total Knee Arthroplasty Roentgenographic Evaluation and Scoring System was used and stress radiographs were obtained at the last follow-up to evaluate PCL function. There was no statistically meaningful difference in radiologic and clinical results between the 2 groups. Radiolucent lines were found for 13 patients radiologically (6 in group 1 and 7 in group 2). No instability as a result of PCL insufficiency required revision surgery on stress radiography at the last follow-up. If an appropriate procedure is performed according to PCL function intraoperatively, CR-TKA can produce a satisfactory result on long-term follow-up. [Orthopedics. 2022;45(4):233-238.].

PPARα-ACOT12 axis is responsible for maintaining cartilage homeostasis through modulating de novo lipogenesis.

Here, in Ppara-/- mice, we found that an increased DNL stimulated the cartilage degradation and identified ACOT12 as a key regulatory factor. Suppressed level of ACOT12 was observed in cartilages of OA patient and OA-induced animal. To determine the role and association of ACOT12 in the OA pathogenesis, we generated Acot12 knockout (KO) (Acot12-/-) mice using RNA-guided endonuclease. Acot12-/- mice displayed the severe cartilage degradation with the stimulation of matrix MMPs and chondrocyte apoptosis through the accumulation of acetyl CoA. Delivery of acetyl CoA-conjugated chitosan complex into cartilage stimulated DNL and cartilage degradation. Moreover, restoration of ACOT12 into human OA chondrocytes and OA-induced mouse cartilage effectively rescued the pathophysiological features of OA by regulating DNL. Taken together, our study suggested ACOT12 as a novel regulatory factor in maintaining cartilage homeostasis and targeting ACOT12 could contribute to developing a new therapeutic strategy for OA.

Mechanoreceptors in Remnant Posterior Cruciate Ligament and Achilles Tendon Allografts After Remnant-Preserving Posterior Cruciate Ligament Reconstruction: Hematoxylin-Eosin and Immunohistochemical Assessments.

BACKGROUND: Mechanoreceptor is a subtype of somatosensory receptor. It conveys extracellular stimuli through intracellular signal conduction via mechanically gated ion channel. It conveys not only kinetic stimuli but also pressure, stretching, touch, and even sound wave. Few studies have determined whether mechanoreceptors are present in Achilles tendon allografts used during remnant-preserving posterior cruciate ligament (PCL) reconstruction (PCLR). PURPOSE/HYPOTHESIS: The purpose was to investigate whether mechanoreceptors are present in remnant tissues of the PCL and allograft tissues after PCLR. It was hypothesized that mechanoreceptors may be present in the remnant PCL tissue of the patients who underwent remnant PCLR technique. STUDY DESIGN: Controlled laboratory study. METHODS: Tissue samples were obtained from 14 participants who had undergone PCLR by means of Achilles tendon allografts (PCLR group) and from 4 healthy controls (control group). Among the PCLR group, 12 patients had undergone a remnant PCLR technique and the remaining 2 patients had undergone a nonremnant PCLR technique. In the PCLR group, we obtained samples during second-look arthroscopy or total knee arthroplasty after PCLR. In the control group, 4 biopsy specimens of normal PCL tissues were obtained from patients who had undergone other arthroscopic procedures. To check the presence of mechanoreceptors, immunohistochemical studies were performed on all biopsy specimens to identify neuronal and neurocytic markers by using monoclonal antibodies against glial fibrillary acidic protein, neuron-specific enolase, neurofilament, and S-100 protein. Only 1 of these markers needed to be positive to prove the presence of mechanoreceptors. RESULTS: Neural tissue analogs, confirmed to be mechanoreceptors with monoclonal antibodies by the Ultraview DAB detection kit, were found in all specimens obtained from the control group. Mechanoreceptors were not found in the allograft specimens. However, remnant PCL tissues were found to have mechanoreceptors in 11 of 12 samples (91.7%). CONCLUSION: The results demonstrate that Achilles tendon allografts lack mechanoreceptors. This study can be used as histological evidence to support the advantage of remnant-preserving techniques for PCLR because they preserve proprioception. CLINICAL RELEVANCE: To preserve proprioception, which leads to better functional outcome, using the remnant technique is a better procedure for PCL reconstruction.

Quantitative assessment of neural elements in a rat model using nerve growth factor after remnant-preserving anterior cruciate ligament reconstruction: a histological and immunofluorescence pilot study.

BACKGROUND: Immunofluorescence analyses of anterior cruciate ligament (ACL) allografts following remnant-preserving ACL reconstruction using Achilles tendon allografts have provided evidence for the presence of neural elements. In this study, we aimed to examine the expression of neural elements and quantify the presence of neural cells in ACL remnants and Achilles allografts using nerve growth factor (NGF) therapy after remnant-preserving ACL reconstruction. METHODS: Experiments were conducted on 5 pairs of rats (approximately 8 weeks old and weighing 320 g at the time of surgery). Longitudinally, split Achilles tendons from the paired rats were freshly frozen and later defrosted with warm saline and allografted onto the right ACL of the other rat that was partially detached at the femoral attachment site. A sham operation was conducted on the left knee to be used as a control. NGF was injected into both knee joints every week for 6 weeks after surgery. The presence of neural cells in the ACL of the sham-operated knee, allografted Achilles tendon, and ACL remnant was examined 6 weeks post-surgery using H and E and immunofluorescent staining. RESULTS: H and E staining did not reveal neural cells in any of the three groups. However, immunofluorescence analysis showed the presence of nestin-positive neural elements in the normal ACL tissues as well as ACL remnants. Additionally, neural elements were examined in 7 of the 8 (87.5%) allograft tissues. Quantitative analysis showed no difference in the number or area of nuclei among the three groups. However, the number and area of neural cells in the Achilles allografts were significantly lower than those in the other two groups (p = 0.000 and p = 0.001, respectively). CONCLUSION: Our observations indicate that ACL remnants promote the new ingrowth and persistence of neural cells. We suggest that the ingrowth of neural elements can support the persistence and new ingrowth of mechanoreceptors, thereby enhancing the functional stability of knee joints. Moreover, the expression of neural cells in the Achilles allografts was lower than that in normal ACL tissues and ACL remnants in the quantitative evaluation, thereby confirming the essential role of ACL remnants in knee joint functionalization.

Microfractures Versus a Porcine-Derived Collagen-Augmented Chondrogenesis Technique for Treating Knee Cartilage Defects: A Multicenter Randomized Controlled Trial.

PURPOSE: The purpose of this study was to evaluate the clinical efficacy and safety of treating patients with a cartilage defect of the knee with microfractures and porcine-derived collagen-augmented chondrogenesis technique (C-ACT). METHODS: One hundred participants were randomly assigned to the control group (n = 48, microfracture) or the investigational group (n = 52, C-ACT). Clinical and magnetic resonance imaging (MRI) outcomes were assessed 12 and 24 months postoperatively for efficacy and adverse events. Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) assessment was used to analyze cartilage tissue repair. MRI outcomes for 50% defect filling and repaired tissue/reference cartilage (RT/RC) ratio were quantified using T2 mapping. Clinical outcomes were assessed using the visual analogue scale (VAS) for pain and 20% improvement, minimal clinically important difference (MCID), and patient acceptable symptom state for Knee Injury and Osteoarthritis Outcome Score (KOOS) and the International Knee Documentation Committee score. RESULTS: MOCART scores in the investigation group showed improved defect repair and filling (P = .0201), integration with the border zone (P = .0062), and effusion (P = .0079). MRI outcomes showed that the odds ratio (OR) for ≥50% defect filling at 12 months was statistically higher in the investigation group (OR 3.984, P = .0377). Moreover, the likelihood of the RT/RC OR becoming ≥1 was significantly higher (OR 11.37, P = .0126) in the investigation group. At 24 months postoperatively, the OR for the VAS 20% improvement rate was significantly higher in the investigational group (OR 2.808, P = .047). Twenty-three patients (52.3%) in the control group and 35 (77.8%) in the investigation group demonstrated more than the MCID of KOOS pain from baseline to 1 year postoperatively, with a significant difference between groups (P = .0116). CONCLUSION: In this multicenter randomized trial, the addition of C-ACT resulted in better filling of cartilage defect of the knee joint. LEVEL OF EVIDENCE: Level Ⅰ, Multicenter Randomized Controlled Trial.

Correction to: Fis1 depletion in osteoarthritis impairs chondrocyte survival and peroxisomal and lysosomal function.

In Fig. 1C, the wrong si-control image was used by mistake.

Correction to: MicroRNA-9 regulates survival of chondroblasts and cartilage integrity by targeting protogenin.

Following publication of the original article [1], the authors reported that Figs. 3 and 6 are incorrect.

Tibial Tubercle Osteotomy vs the Extensile Medial Parapatellar Approach in Revision Total Knee Arthroplasty: Is Tibial Tubercle Osteotomy a Harmful Approach?

BACKGROUND: As the frequency of total knee arthroplasty (TKA) is increasing, long-term follow-up of patients has become essential, and the frequency of revision total knee arthroplasty (R-TKA) due to the occurrence of various complications has also increased. There is controversy regarding which approach has minimal complications and an adequate visual field in R-TKA. Therefore, we compared the clinical and radiological results between the extensile medial parapatellar (EMP) approach and tibial tubercle osteotomy (TTO) for R-TKA. METHODS: Between March 1, 2000, and December 31, 2015, we compared 35 patients who underwent the EMP approach and 31 who underwent the TTO approach for R-TKA. In this study, the preoperative range of motion (ROM) was an important criterion for the choice of approach in R-TKA. The EMP approach was applied to patients with a ROM above 60°. The TTO approach was applied to patients with knee flexion limited to 0°-30°. We clinically assessed knee ROM, Knee Society scores, and Hospital for Special Surgery scores at the time of the last follow-up. We radiographically measured femorotibial alignment and patellar height. We also examined the complication rates. The average length of the TTO was 1.0 × 2.5 cm × 10 cm. We used 3 or more 3.5-mm half-threaded screws. RESULTS: The mean postoperative ROM of the knee joint at the time of the last follow-up was 103° (flexion contracture 5° and further flexion 108°) in the group that underwent the EMP approach and 101° (flexion contracture 4° and further flexion 109°) in the group that underwent the TTO approach. The mean Knee Society scores were 86 (71-96) and 85 (72-94), and the mean Hospital for Special Surgery scores were 82 (70-93) and 83 (68-92) for the 2 groups, respectively, with no statistically significant difference. The mean femorotibial angles were 0.6° (±3.3°) and 0.1° (±2.9°), and the mean Insall-Salvati ratios were 1.0 (±0.34) and 0.8 (±0.14), respectively, with no statistically significant difference. The group that underwent TTO achieved bone union at an average of 11.8 weeks after surgery. In the group that underwent the EMP approach, 2 patients had extensor lag of more than 10°. In the group that underwent TTO, 2 subjects had skin necrosis at the operative site. CONCLUSION: The clinical and radiological outcomes were similar in the 2 groups after R-TKA. To increase the ROM and obtain adequate exposure, TTO is also considered a useful surgical approach. However, complications related to TTO should be minimized. LEVEL OF EVIDENCE: Therapeutic level III, retrospective comparative study.

Correction: HIF-1α:CRAT:miR-144-3p axis dysregulation promotes osteoarthritis chondrocyte apoptosis and VLCFA accumulation.

[This corrects the article DOI: 10.18632/oncotarget.20615.].

The CH25H-CYP7B1-RORα axis of cholesterol metabolism regulates osteoarthritis.

Osteoarthritis-the most common form of age-related degenerative whole-joint disease1-is primarily characterized by cartilage destruction, as well as by synovial inflammation, osteophyte formation and subchondral bone remodelling2,3. However, the molecular mechanisms that underlie the pathogenesis of osteoarthritis are largely unknown. Although osteoarthritis is currently considered to be associated with metabolic disorders, direct evidence for this is lacking, and the role of cholesterol metabolism in the pathogenesis of osteoarthritis has not been fully investigated4-6. Various types of cholesterol hydroxylases contribute to cholesterol metabolism in extrahepatic tissues by converting cellular cholesterol to circulating oxysterols, which regulate diverse biological processes7,8. Here we show that the CH25H-CYP7B1-RORα axis of cholesterol metabolism in chondrocytes is a crucial catabolic regulator of the pathogenesis of osteoarthritis. Osteoarthritic chondrocytes had increased levels of cholesterol because of enhanced uptake, upregulation of cholesterol hydroxylases (CH25H and CYP7B1) and increased production of oxysterol metabolites. Adenoviral overexpression of CH25H or CYP7B1 in mouse joint tissues caused experimental osteoarthritis, whereas knockout or knockdown of these hydroxylases abrogated the pathogenesis of osteoarthritis. Moreover, retinoic acid-related orphan receptor alpha (RORα) was found to mediate the induction of osteoarthritis by alterations in cholesterol metabolism. These results indicate that osteoarthritis is a disease associated with metabolic disorders and suggest that targeting the CH25H-CYP7B1-RORα axis of cholesterol metabolism may provide a therapeutic avenue for treating osteoarthritis.

Comparison of Modified Transtibial and Anteromedial Portal Techniques in Anatomic Single-Bundle ACL Reconstruction.

The purpose of this study was to compare the clinical, 3-dimensional computed tomography, magnetic resonance imaging, and second-look arthroscopic findings of the modified transtibial technique with those of the anteromedial portal technique in single-bundle anterior cruciate ligament reconstruction (SB-ACLR). Among patients who underwent SB-ACLR from February 2012 to May 2014, 95 patients with a minimum of 36 months of follow-up were included in this retrospective study. Forty-five patients underwent a reconstruction using the modified transtibial technique. Fifty patients underwent a reconstruction using the anteromedial portal technique. Clinical scores and stabilities were recorded preoperatively and at final follow-up. All patients had postoperative computed tomography and the computed tomography parameters, including tunnel position and graft obliquity, evaluated. Additionally, postoperative magnetic resonance imaging and second-look arthroscopy were performed. On the basis of the functional and stability outcomes, all of the patients showed significant improvement after SB-ACLR, with no significant differences existing between the 2 groups (P>.05). Tunnel position and obliquity were not significantly different between the 2 groups (P>.05). There were no statistically significant differences between the 2 groups regarding the magnetic resonance imaging and second-look arthroscopy findings (P>.05). The tunnel characteristics and clinical results of the 2 techniques were comparable. Given the several advantages of the modified transtibial technique, including its simplicity and patients' greater activity level, it is suitable for anatomic SB-ACLR. [Orthopedics. 2019; 42(2):83-89.].

RNA-binding protein ZFP36L1 regulates osteoarthritis by modulating members of the heat shock protein 70 family.

Osteoarthritis (OA) is a whole-joint disease characterized by cartilage destruction and other whole-joint pathological changes. There is currently no effective disease-modifying therapy. Here we investigate the post-transcriptional mRNA regulation of OA-modulating proteins in chondrocytes and show that the ZFP36 family member, ZFP36L1, is specifically upregulated in OA chondrocytes and OA cartilage of humans and mice. Adenovirus-mediated overexpression of ZFP36L1 alone in mouse knee-joint tissue does not modulate OA pathogenesis. However, genetic ablation or silencing of Zfp36l1 significantly abrogates experimental OA in mice. Knockdown of Zfp36l1 increases the mRNA expression of two heat shock protein 70 (HSP70) family members, which act as its direct targets. Furthermore, overexpression of HSPA1A in joint tissues protects mice against experimental OA by inhibiting chondrocyte apoptosis. Our results indicate that the RNA-binding protein, ZFP36L1, regulates HSP70 family members that appear to protect against OA pathogenesis by inhibiting chondrocyte apoptosis.

Critical role for arginase II in osteoarthritis pathogenesis.

OBJECTIVE: Osteoarthritis (OA) appears to be associated with various metabolic disorders, but the potential contribution of amino acid metabolism to OA pathogenesis has not been clearly elucidated. Here, we explored whether alterations in the amino acid metabolism of chondrocytes could regulate OA pathogenesis. METHODS: Expression profiles of amino acid metabolism-regulating genes in primary-culture passage 0 mouse chondrocytes were examined by microarray analysis, and selected genes were further characterised in mouse OA chondrocytes and OA cartilage of human and mouse models. Experimental OA in mice was induced by destabilisation of the medial meniscus (DMM) or intra-articular (IA) injection of adenoviruses expressing catabolic regulators. The functional consequences of arginase II (Arg-II) were examined in Arg2-/- mice and those subjected to IA injection of an adenovirus encoding Arg-II (Ad-Arg-II). RESULTS: The gene encoding Arg-II, an arginine-metabolising enzyme, was specifically upregulated in chondrocytes under various pathological conditions and in OA cartilage from human patients with OA and various mouse models. Adenovirus-mediated overexpression of Arg-II in mouse joint tissues caused OA pathogenesis, whereas genetic ablation of Arg2 in mice (Arg2-/-) abolished all manifestations of DMM-induced OA. Mechanistically, Arg-II appears to cause OA cartilage destruction at least partly by upregulating the expression of matrix-degrading enzymes (matrix metalloproteinase 3 [MMP3] and MMP13) in chondrocytes via the nuclear factor (NF)-κB pathway. CONCLUSIONS: Our results indicate that Arg-II is a crucial regulator of OA pathogenesis in mice. Although chondrocytes of human and mouse do not identically, but similarly, respond to Arg-II, our results suggest that Arg-II could be a therapeutic target of OA pathogenesis.

The lncRNA, Nespas, Is Associated with Osteoarthritis Progression and Serves as a Potential New Prognostic Biomarker.

INTRODUCTION: In this article, we explored the hypothesis that the long noncoding RNA, Nespas, promotes osteoarthritis (OA) by supporting abnormal lipid metabolism in human chondrocytes. MATERIALS AND METHODS: Human articular chondrocytes from osteoarthritis patients were used and expression level of Nespas were determined by real-time polymerase chain reaction. Introduction of Nespas and Nespas-associated genes/miRNAs were performed by using a lentiviral system. The effect of Nespas on mitochondrial function was determined by staining mitochondria and analyzing mitopotential and mitochondrial genes. Moreover, to identify the responsible molecules in Nespas-induced pathogenesis, profiling of peroxisomal genes and miRNAs were applied and interactome analysis was performed. RESULTS: Highly elevated levels of Nespas and Acyl-CoA synthetase 6 (ACSL6) were observed in OA patients. Both Nespas overexpression and ACSL6 upregulation into human chondrocytes induced typical OA characteristics, such as downregulation of type II collagen; upregulation of type I collagen, metalloproteinase 13, and caspase-1 and -3; and dysfunction of mitochondria and peroxisome. Co-expression of Nespas and ACSL6 siRNA reduced caspase-1 and -3 levels. Moreover, Nespas overexpression significantly suppressed levels of miR-291a-3p, -196a-5p, -23a-3p, -24-3p, and let-7a-5p, and these miRs are known to potentially target ACSL6 according to ingenuity pathway analysis. We also confirmed that these miRs were significantly suppressed in human OA chondrocytes. Overexpression of miR-291a-3p, -196a-5p, -23a-3p, -24-3p, or let-7a-5p in the presence of Nespas suppressed levels of ACSL6, caspase-1 and -3. DISCUSSION: Overall, we suggest that elevated Nespas level in OA are associated with OA pathogenesis by suppressing miRs targeting ACSL6 and subsequent ACSL6 upregulation.

Pseudoaneurysm Formation due to Popliteal Artery Injury Caused by Drilling during Medial Opening Wedge High Tibial Osteotomy.

We report a case of 53-year-old woman with an injured popliteal artery due to excessive drilling with a drill bit during medial opening wedge high tibial osteotomy (MOWHTO). Pseudoaneurysm was diagnosed three days after surgery and confirmed by urgent computed tomography (CT) angiography. Open vascular surgery with resection of the perivascular hematoma and end-to-end anastomosis using ipsilateral saphenous vein interposition graft was performed. CT angiography at 8 months postoperatively showed that blood flow was maintained without obstruction of the graft site and active dorsiflexion of the foot was possible. To reduce neurovascular injury during MOWHTO, it is important not to drill the far cortex at the proximal part of the osteotomy site when using a drill bit, and the metal should be positioned posteromedially as much as possible.

Suppression of ABCD2 dysregulates lipid metabolism via dysregulation of miR-141:ACSL4 in human osteoarthritis.

Even though increasing evidence indicates the importance of peroxisomal lipid metabolism in regulating biological and pathological events, its involvement in cartilage development has not been well studied. Here, we identified the importance of peroxisomal function, particularly the functional integrity of ABCD2, in the pathogenesis of osteoarthritis (OA). Knockdown of ABCD2 in OA chondrocytes induced the accumulation of very long chain fatty acids (VLCFAs) and apoptotic cell death. Moreover, knockdown of ABCD2 altered profiles of miRNAs that affect the expression level of ACSL4, a known direct regulator of lipid metabolism. Suppression of ACSL4 in human chondrocytes-induced VLCFA accumulation, MMP-13 expression, and apoptotic cell death. In vivo morph-down of the ACSL4 homologue in zebrafish resulted in significant defects in cartilage development and in vivo knockdown of ACSL4 in cartilage tissue of an OA model mice promoted severe cartilage degradation. In summary, to the best of our knowledge, this is the first report suggesting that the regulatory network among peroxisomal ABCD2:ACSL4:VLCFA serves as a novel regulator of cartilage homeostasis, and these data may provide novel insights into the role of peroxisomal fatty acid metabolism in pathogenesis of human OA. SIGNIFICANCE OF THE STUDY: Our study indicates that peroxisomal dysfunction is closely related to OA pathogenesis. Particularly, the functional integrity of ABCD2 may play an important role in OA pathogenesis via the accumulation of VLCFAs and stimulation of apoptotic death through altering profiles of miRNAs that target ACSL4. Our findings suggest that targeting the regulatory network among the peroxisomal ABCD2:ACSL4:VLCFA axis may provide a new potential therapeutic strategy for OA pathogenesis.