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.].

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.

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.

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.].

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.

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.

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.

Alleviation of Murine Osteoarthritis by Cartilage-Specific Deletion of IκBζ.

OBJECTIVE: IκBζ, an atypical IκB family member, regulates gene expression in the nucleus as a transcriptional cofactor. Although IκBζ has been extensively studied in the immune system, its specific roles in osteoarthritis (OA) are currently unknown. The objective of this study was to investigate the potential role of IκBζ in chondrocyte catabolism and OA pathogenesis. We also determined the molecular mechanism underlying its relationship to the transcription factor NF-κB. METHODS: We determined expression levels of IκBζ in mouse chondrocytes treated with interleukin-1ß (IL-1ß), in human OA cartilage, and in mouse experimental OA cartilage. Adenovirus-mediated overexpression and small interfering RNA knockdown of IκBζ were performed to determine the impact of IκBζ on catabolic gene expression in vitro. Cartilage-specific IκBζ-transgenic and -knockout mice were generated and used for in vivo studies. Experimental and spontaneous OA were induced by surgical destabilization of the medial meniscus and by aging, respectively. Coimmunoprecipitation assay was used to examine the association between IκBζ and NF-κB subunits. RESULTS: IκBζ was highly up-regulated in chondrocytes in response to IL-1ß and in OA cartilage of human and mouse knee joints. Overexpression of IκBζ in chondrocytes promoted spontaneous OA development by activating chondrocyte catabolism. Genetic ablation of IκBζ in chondrocytes abolished catabolic gene induction by IL-1ß and protected against the development of experimental OA. IκBζ formed complexes with NF-κB members to regulate catabolic factor expression. CONCLUSION: These findings demonstrate a critical role for IκBζ in OA pathogenesis. Inhibition of IκBζ function might be an effective therapeutic approach for OA treatment.

A case of bilateral revision total knee arthroplasty using distal femoral allograft-prosthesis composite and femoral head allografting at the tibial site with a varus-valgus constrained prosthesis: ten-year follow up.

BACKGROUND: We report the successful use of allograft-prosthesis composite (APC) and structural femoral head allografting in the bilateral reconstruction of large femoral and tibial uncontained defects during revision total knee arthroplasty (RTKA). CASE PRESENTATION: A 67-year-old female with degenerative arthritis underwent bilateral total knee arthroplasty (TKA) using the Press Fit Condylar (PFC) modular knee system at our clinic in March, 1996. At 8 years postoperatively, the patient presented with painful, bilateral varus knees, with swelling, limited passive range of motion (ROM), and severe instability. We treated to reconstruct both knee using a femoral head allograft at the tibial site, a structural distal femoral allograft at the femoral site, and a varus-valgus constrained (VVC) prosthesis with cement. At the 10-year follow up, we found no infection, graft failure, loosening of implants, in spite of using massive bilateral structural femoral head allografts in RTKA. CONCLUSION: The use of APC enabled a stable and durable reconstruction in this uncommon presentation with large femoral bone deficiencies encountered during a RTKA.

Estrogen-related receptor γ causes osteoarthritis by upregulating extracellular matrix-degrading enzymes.

The estrogen-related receptor (ERR) family of orphan nuclear receptor is composed of ERRα, ERRß, and ERRγ, which are known to regulate various isoform-specific functions under normal and pathophysiological conditions. Here, we investigate the involvement of ERRs in the pathogenesis of osteoarthritis (OA) in mice. Among ERR family members, ERRγ is markedly upregulated in cartilage from human OA patients and various mouse models of OA. Adenovirus-mediated overexpression of ERRγ in mouse knee joint or transgenic expression of ERRγ in cartilage leads to OA. ERRγ overexpression in chondrocytes directly upregulates matrix metalloproteinase (MMP)-3 and MMP13, which are known to play crucial roles in cartilage destruction in OA. In contrast, genetic ablation of Esrrg or shRNA-mediated downregulation of Esrrg in joint tissues abrogates experimental OA in mice. Our results collectively indicate that ERRγ is a novel catabolic regulator of OA pathogenesis.

Clinical and radiological results of cruciate-retaining total knee arthroplasty with the NexGen®-CR system: comparison of patellar resurfacing versus retention with more than 14 years of follow-up.

BACKGROUND: The purpose of this study is to analyze clinical and radiological outcomes of patients (with a minimum of 14 years of follow-up) who underwent cruciate-retaining (CR) total knee arthroplasty (TKA) using a NexGen®-CR, comparing a patellar resurfacing group with a patellar retention group. METHODS: From June 1996 to April 2002, 116 cases of TKA using a NexGen®-CR who had at least 14 years of follow-up were enrolled in this study. Among them, 68 cases had patellar resurfacing and 48 had patellar retention. The average follow-up period was 14.8 years (14.1-18.7). Clinical scores and range of motion (ROM) were evaluated preoperatively and at the last follow-up in all patients. The Hospital for Special Surgery (HSS) score, Knee Society Score (KSS), Western Ontario and MacMaster Universities Osteoarthritis (WOMAC) score, and a new patellar score were assessed. Radiological evaluations are done by analyzing the tibiofemoral angle, loosening, and a radiolucent line on the radiograph by American Knee Society Roentgen Graphic Evaluation. RESULTS: The average HSS score of both the patellar resurfacing group and retention group increased from 42.3 and 41.2 preoperatively to 90.2 and 90.8 at the last follow-up, respectively. The KSS, WOMAC score, patellar score, and knee joint ROM also improved significantly in both groups. However, there were no significant differences in clinical results between the two groups. On the radiological evaluation, the tibiofemoral angle in both groups had improved from varus 7.8° and 7.2° preoperative to valgus 4.9° and 4.8°, respectively. The average angles of α, ß, γ, and δ were 94.1°, 90.4°, 3.2°, and 87.8° in the patellar resurfacing group and 94.4°, 89.8°, 3.3°, and 88.1° in the patellar retention group, respectively. A radiolucent line shown on radiograph was noted in a total of seven cases, three in the patellar resurfacing group and four in the patellar retention group. In the patellar resurfacing group, among the seven zones on the tibia radiograph, all cases were located at the medial side of tibia and two cases were in zone 1 and one case in zone 2, and in the patellar retention group, three cases were in zone 1 and 1 case was in zone 2, also located on the same side. CONCLUSIONS: We achieved satisfactory clinical and radiological outcomes on long-term follow-up when performing TKAs with a NexGen®-CR. There was no significant difference in clinical or radiological results between the patellar resurfacing and retention groups in our study.

Immunohistochemical and immunocytochemical study of mechanoreceptors in anterior cruciate ligament reconstruction with the remnant-preserving technique using Achilles tendon allografts.

BACKGROUND: Attempts have been made to validate the significance of remnant preservation with anterior cruciate ligament (ACL) reconstruction using immunohistochemical and immunocytochemical techniques. The purpose of this study was to examine the expression of mechanoreceptors in the remnant tissue of ACL reconstruction performed with the remnant-preserving technique. METHODS: Tissue samples were obtained from 10 patients who underwent ACL reconstruction with the remnant-preserving technique. The specimens were obtained from remnant ACL tissue and Achilles allografts superficially and at the tibial attachment. The control group consisted of three normal ACLs procured from young males who underwent partial meniscectomy. Tissues and cells from the ACL remnants and Achilles allografts were characterized using hematoxylin and eosin (H&E) staining and immunohistochemical, immunocytochemical, and immunoblotting assays. In particular, the sensitivity of neural cell validation was improved using nerve growth factor (NGF) to stimulate the expression of neural cells. RESULTS: The results are summarized as follows. (1) In H&E staining and immunohistochemical assays, no neural cells were detected in remnant or allograft tissue. (2) In the immunocytochemical study, neural cells were detected in remnant tissue. (3) The increased proliferation of remnant ACL cells with NGF treatment suggested their identity as neural cells. (4) NGF treatment also stimulated protein and RNA expression of Nestin (a specific marker for neural cells) in remnant ACL cells. CONCLUSIONS: The improved immunocytochemical methodology proved useful. Although mechanoreceptors were detected relatively less frequently than expected, the authors consider that this finding does not negate the necessity of remnant-preserving ACL reconstruction.

Inhibition of BATF/JUN transcriptional activity protects against osteoarthritic cartilage destruction.

OBJECTIVE: The basic leucine zipper transcription factor, ATF-like (BATF), a member of the Activator protein-1 family, promotes transcriptional activation or repression, depending on the interacting partners (JUN-B or C-JUN). Here, we investigated whether the BATF/JUN complex exerts regulatory effects on catabolic and anabolic gene expression in chondrocytes and contributes to the pathogenesis of osteoarthritis (OA). METHODS: Primary cultured mouse chondrocytes were treated with proinflammatory cytokines (interleukin-1ß, IL-6 or tumour necrosis factor-α) or infected with adenoviruses carrying the Batf gene (Ad-Batf). Expression of BATF and JUN was examined in human and mouse experimental OA cartilage samples. Experimental OA in mice was induced by destabilisation of the medial meniscus or intra-articular injection of Ad-Batf. The chromatin immunoprecipitation assay was used to examine the binding of BATF and JUN to the promoter regions of candidate genes. RESULTS: Overexpression of BATF, which forms a heterodimeric complex with JUN-B and C-JUN, induced upregulation of matrix-degrading enzymes and downregulation of cartilage matrix molecules in chondrocytes. BATF expression in mouse joint tissues promoted OA cartilage destruction, and conversely, knockout of Batf in mice suppressed experimental OA. Pharmacological inhibition of BATF/JUN transcriptional activity reduced the expression of matrix-degrading enzymes and protected against experimental OA in mice. CONCLUSIONS: BATF/JUN-B and BATF/C-JUN complexes play important roles in OA cartilage destruction through regulating anabolic and catabolic gene expression in chondrocytes. Our findings collectively support the utility of BATF as a therapeutic target for OA.

Prophylaxis for Venous Thromboembolism Following Total Knee Arthroplasty: A Survey of Korean Knee Surgeons.

PURPOSE: The purpose of this study is to provide information on the actual status and prevailing trend of prophylaxis for venous thromboembolism (VTE) following total knee arthroplasty (TKA) in South Korea. MATERIALS AND METHODS: The Korean Knee Society (KKS) developed a questionnaire with 6 clinical questions on VTE. The questionnaire was distributed to all members of KKS by both postal and online mail. Participants were asked to supply details on their specialty and to select methods of prophylaxis they employ. Of the total members of KKS, 27.9% participated in the survey. RESULTS: The percentage of surgeons who routinely performed prophylaxis for VTE was 60.4%; 19.4% performed prophylaxis depending on the patient's health condition; and the remaining 20.2% never implemented prophylaxis after surgery. The common prophylactic methods among the responders were compression stocking (72.9%), pneumatic leg compression (63.3%), perioral direct factor Xa inhibitor (46.9%), and low-molecular-weight heparin (39.5%). For the respondents who did not perform prophylaxis, the main reason (51.5%) was the low risk of postoperative VTE considering the low incidences in Asians. CONCLUSIONS: The present study involving members of the KKS will help to comprehend the actual status of VTE prevention in South Korea. The results of this study may be useful to design VTE guidelines appropriate for Koreans in the future.

The Fate of Allogeneic Femoral Head Bone Grafts Using Varus-Valgus Constrained Total Knee Arthroplasty in Neuropathic Joints.

BACKGROUND: This study was conducted to assess the clinical and radiological results of total knee arthroplasty (TKA) with an allogeneic bone graft using varus-valgus constrained (VVC) prostheses in knees with severe bone defects and unstable neuropathy. METHODS: This study included 20 knees of 16 patients who underwent TKA between August 2001 and January 2006 due to unstable knees with severe bone destruction resulting from neuropathic arthritis. At the time of surgery, the mean age of the patients was 56 years. The mean length of the follow-up period was 10.7 years. A VVC condylar prosthesis was used with an allogeneic femoral head graft to reconstruct large bony defects. Clinical results were evaluated using the Hospital for Special Surgery, Knee Society function, and Western Ontario and McMaster Universities Osteoarthritis scores. Three-dimensional computed tomography was used to evaluate the radiological parameters, which included the tibiofemoral angle, loosening or osteolysis of components, and incorporation of the bone graft. RESULTS: The preoperative mean Hospital for Special Surgery, Knee Society function, and Western Ontario and McMaster Universities Osteoarthritis scores were 40.5, 43.2, and 78.3, respectively, and these scores improved to 86.0, 64.6, and 33.8, respectively at the final follow-up. The mean postoperative alignment was 6.1° of valgus angulation. One knee had instability, another knee had partial bony absorption, which was confirmed using 3-dimensional computed tomography, and the other 18 cases (90%) had satisfactory results. No cases experienced radiolucency, fracture, or infection. CONCLUSIONS: TKA with an allogeneic bone graft using a VVC prosthesis provides a viable option for the treatment of severe bone defects with soft-tissue insufficiency in neuropathic knee arthropathy.

Arthroscopic Bioabsorbable Screw Fixation of Unstable Osteochondritis Dissecans in Adolescents: Clinical Results, Magnetic Resonance Imaging, and Second-Look Arthroscopic Findings.

BACKGROUND: This study aimed to evaluate the clinical and radiological outcomes of arthroscopic bioabsorbable screw fixation in osteochondritis dissecans (OCD) in adolescent patients with unstable lesions causing pain. METHODS: The study included 11 patients (10 males and 1 female) with OCD who underwent arthroscopic bioabsorbable screw fixation between July 2007 and February 2014 and were available for follow-up for more than 12 months. The mean age at diagnosis was 16.3 years (range, 11 to 19 years), and the average follow-up period was 51 months (range, 12 to 91 months). Clinical results were evaluated using the Knee Injury and Osteoarthritis Outcome Score (KOOS), Lysholm knee score, and International Knee Documentation Committee (IKDC) score measured before surgery and at follow-up. Functional evaluation was made using the Tegner activity scale. Magnetic resonance imaging (MRI) and second-look arthroscopy were performed at the 12-month follow-up. RESULTS: Between the preoperative assessment and follow-up, improvements were seen in the KOOS (range, 44.9 to 88.1), Lysholm knee score (range, 32.6 to 82.8), and IKDC score (range, 40.8 to 85.6). The Tegner activity scale also improved from 2.8 to 6.1. Based on postoperative MRI, there were eight Dipaola grade I cases and three grade II cases. No complications due to fixation failure developed in any case. Second-look arthroscopy at 12 months postoperatively revealed that the lesion was covered with cartilage in all cases. CONCLUSIONS: For unstable OCD lesions causing pain in adolescents, arthroscopic bioabsorbable screw fixation provided favorable outcomes with reduced pain and restoration of movement. Therefore, it should be considered as an effective treatment for OCD.

Pleiotropic roles of metallothioneins as regulators of chondrocyte apoptosis and catabolic and anabolic pathways during osteoarthritis pathogenesis.

OBJECTIVE: The zinc-ZIP8-MTF1 axis induces metallothionein (MT) expression and is a catabolic regulator of experimental osteoarthritis (OA) in mice. The main aim of the current study was to explore the roles and underlying molecular mechanisms of MTs in OA pathogenesis. METHODS: Experimental OA in mice was induced by destabilisation of the medial meniscus or intra-articular injection of adenovirus carrying a target gene (Ad-Zip8, Ad-Mtf1, Ad-Epas1, Ad-Nampt, Ad-Mt1 or Ad-Mt2) into wild type, Zip8fl/fl; Col2a1-Cre, Mtf1fl/fl; Col2a1-Cre and Mt1/Mt2 double knockout mice. Primary cultured mouse chondrocytes were infected with Ad-Mt1 or Ad-Mt2, and gene expression profiles analysed via microarray and reverse transcription-PCR. Proteins in human and mouse OA cartilage were identified via immunostaining. Chondrocyte apoptosis in OA cartilage was determined using terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labelling (TUNEL). RESULTS: MTs were highly expressed in human and mouse OA cartilage. Hypoxia-inducible factor 2α, nicotinamide phosphoribosyltransferase and several proinflammatory cytokine pathways, as well as the zinc-ZIP8-MTF1 axis were identified as upstream regulators of MT expression. Genetic deletion of Mt1 and Mt2 enhanced cartilage destruction through increasing chondrocyte apoptosis. Unexpectedly, aberrant overexpression of MT2, but not MT1, induced upregulation of matrix-degrading enzymes and downregulation of matrix molecules through nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1) activation, ultimately leading to OA. CONCLUSIONS: MTs play an antiapoptotic role in post-traumatic OA. However, aberrant and chronic upregulation of MT2 triggers an imbalance between chondrocyte anabolism and catabolism, consequently accelerating OA development. Our findings collectively highlight pleiotropic roles of MTs as regulators of chondrocyte apoptosis as well as catabolic and anabolic pathways during OA pathogenesis.