Distal embolization resulting from carotid angioplasty and stenting (CAS) occurs mainly in the cerebral hemisphere. We report a case of ophthalmic artery occlusion after carotid revascularization. A 75-year old man received emergency CAS for cervical internal carotid artery occlusion. Two months later, the patient was readmitted for decreased visual acuity. We found ophthalmic artery occlusion that was not noticed soon after CAS. Although ophthalmic artery occlusion after CAS is rare, endovascular neurosurgeons should be aware of this potential complication.
Carotid angioplasty and stenting; Embolization; Ophthalmic artery occlusion
The limitations of medical management of symptomatic intracranial arterial stenosis (ICS) have prompted development of new strategies, including endovascular treatment. However, stenting of symptomatic ICS remains investigational. Here, we have reported and analyzed a series of 19 endovascular procedures involving placement of a Wingspan stent.
We conducted a retrospective review of a series of ICS in which patients were treated with percutaneous transarterial balloon angioplasty and stent placement (PTAS). Patients included in the study were diagnosed as symptomatic ICS between May 2010 and September 2011.
Nineteen patients (median age, 65 years; 12 males, seven women) were treated with the Wingspan stent system for symptomatic ICS ranging from 50% to 99%. The technical success rate was 100%. The location of ICS included the internal carotid (n = 5; 1 petrous, 3 cavernous, and 1 clinoid segments), vertebral (n = 1; V4 segment), basilar (n = 1), and middle cerebral (n = 12; 9 M1, 3 M2) arteries. There was no occurrence of procedure-related mortality. Periprocedural morbidity occurred in two cases (10.5%), including carotid-cavernous fistula (n = 1) and subarachnoid hemorrhage (n = 1). No ipsilateral stroke was recorded beyond 30 days during a mean follow-up period of 13.2 months (range 9-19 months). Restenosis (> 50%) was observed in one patient (6.3%), who was asymptomatic, on follow-up imaging.
Wingspan stent for symptomatic ICS can be performed with a high rate of technical success and acceptable periprocedural morbidity rates. Our initial experience indicates that this procedure represents a viable treatment option for this patient population.
Intracranial stenosis; Angioplasty; Stent implantation; Wingspan stent
Dual origin and fenestration of the vertebral artery (VA) are very rare anomalies. Understanding of these variations, however, is important because they can be misdiagnosed as a VA dissection. A 42-year-old woman presented with motor weakness and sensory disturbance of the right upper extremity. Radiologic evaluations showed ectatic change in the right VA and an arteriovenous fistula between the right VA and the vertebral vein. We decided on endovascular occlusion of the proximal right VA and its fistulous portion. During the endovascular procedure, we had misunderstood the dual origin and fenestration of the VA as a dissection. Thus, failure to recognize these anomalies might result in unnecessary anticoagulation or therapeutic intervention. Clinicians should be alert to such VA variations when making a diagnosis and when planning any intervention or surgery involving the proximal VA.
Dissection; Dual origin; Fenestration; Vertebral artery
The purpose of this report is to describe our surgical experiences in the treatment of cerebral decompression with in situ floating resin cranioplasty. We included in this retrospective study 7 patients who underwent in situ floating resin cranioplasty for cerebral decompression between December 2006 and March 2008. Of these patients, 3 patients had traumatic brain injury, 3 cerebral infarction, and one subarachnoid hemorrhage due to aneurysmal rupture. In situ floating resin cranioplasty for cerebral decompression can reduce complications related to the absence of a bone flap and allow reconstruction by secondary cranioplasty without difficulty. Furthermore, it provides cerebral protection and selectively eliminates the need for secondary cranioplasty in elderly patients or patients who have experienced unfavorable outcome.
Decompressive craniectomy; Floating; Resin cranioplasty
Excessive reactive oxygen species (ROS) generated from abnormal cellular process lead to various human diseases such as inflammation, ischemia, and Parkinson’s disease (PD). Sensitive to apoptosis gene (SAG), a RING-FINGER protein, has anti-apoptotic activity and anti-oxidant activity. In this study, we investigate whether Tat-SAG, fused with a Tat domain, could protect SH-SY5Y neuroblastoma cells against 1-methyl-4-phenylpyridinium (MPP+) and dopaminergic (DA) neurons in the substantia nigra (SN) against 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP) toxicity. Western blot and immunohistochemical analysis showed that, unlike SAG, Tat-SAG transduced efficiently into SH-SY5Y cells and into the brain, respectively. Tat-SAG remarkably suppressed ROS generation, DNA damage, and the progression of apoptosis, caused by MPP+ in SH-SY5Y cells. Also, immunohistochemical data using a tyrosine hydroxylase antibody and cresyl violet staining demonstrated that Tat-SAG obviously protected DA neurons in the SN against MPTP toxicity in a PD mouse model. Tat-SAG-treated mice showed significant enhanced motor activities, compared to SAG- or Tat-treated mice. Therefore, our results suggest that Tat-SAG has potential as a therapeutic agent against ROS-related diseases such as PD.
dopaminergic neuron; Parkinson’s disease; protein transduction domain; reactive oxygen species; sensitive to apoptosis gene
In this study, we determined how rosiglitazone (RSG) differentially affected hippocampal neurogenesis in mice fed a low-fat diet (LFD) or high-fat diet (HFD; 60% fat). LFD and HFD were given to the mice for 8 weeks. Four weeks after initiating the LFD and HFD feeding, vehicle or RSG was administered orally once a day to both groups of mice. We measured cell proliferation and neuroblast differentiation in the subgranular zone of the dentate gyrus using Ki67 and doublecortin (DCX), respectively, as markers. In addition, we monitored the effects of RSG on the levels of DCX and brain-derived neurotrophic factor (BDNF) in hippocampal homogenates. At 8 weeks after the LFD feeding, the numbers of Ki67- and DCX-positive cells as well as hippocampal levels of DCX and BDNF were significantly decreased in the RSG-treated group compared to the vehicle-treated animals. In contrast, the numbers of Ki67- and DCX-positive cells along with hippocampal levels of DCX and BDNF in the HFD fed mice were significantly increased in the RSG-treated mice compared to the vehicle-treated group. Our data demonstrate that RSG can modulate the levels of BDNF, which could play a pivotal role in cell proliferation and neuroblast differentiation in the hippocampal dentate gyrus.
brain-derived neurotrophic factor; dentate gyrus; high-fat diet; rosiglitazone
Paraoxonase 1 (PON1) is an antioxidant enzyme which plays a central role in various diseases. However, the mechanism and function of PON1 protein in inflammation are poorly understood. Since PON1 protein alone cannot be delivered into cells, we generated a cell permeable PEP-1-PON1 protein using protein transduction domains, and examined whether it can protect against cell death in lipopolysaccharide (LPS) or hydrogen peroxide (H2O2)-treated Raw 264.7 cells as well as mice with 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced skin inflammation. We demonstrated that PEP-1-PON1 protein transduced into Raw 264.7 cells and markedly protected against LPS or H2O2-induced cell death by inhibiting cellular reactive oxygen species (ROS) levels, the inflammatory mediator’s expression, activation of mitogen-activated protein kinases (MAPKs) and cellular apoptosis. Furthermore, topically applied PEP-1-PON1 protein ameliorates TPA-treated mice skin inflammation via a reduction of inflammatory response. Our results indicate that PEP-1-PON1 protein plays a key role in inflammation and oxidative stress in vitro and in vivo. Therefore, we suggest that PEP-1-PON1 protein may provide a potential protein therapy against oxidative stress and inflammation.
In order to clarify the optimal timing for peripheral blood stem cell (PBSC) collection, PBSC collection records of 323 children who were scheduled to undergo autologous stem cell transplantation from two study periods differing in the timing of PBSC collection were analyzed. In the early study period (March 1998 to August 2007, n=198), PBSC collection was initiated when the peripheral WBC count exceeded 1,000/µL during recovery from chemotherapy. Findings in this study period indicated that initiation of PBSC collection at a higher WBC count might result in a greater CD34+ cell yield. Therefore, during the late study period (September 2007 to December 2012, n=125), PBSC collection was initiated when the WBC count exceeded 4,000/µL. Results in the late study period validated our conclusion from the early study period. Collection of a higher number of CD34+ cells was associated with a faster hematologic recovery after transplant in the late study period. Initiation of PBSC collection at WBC count > 4,000/µL was an independent factor for a greater CD34+ cell yield. In conclusion, PBSC collection at a higher WBC count is associated with a greater CD34+ cell yield, and consequently a faster hematologic recovery after transplant.
High-Dose Chemotherapy; Autologous Stem Cell Transplantation; Peripheral Blood Stem Cell Collection
Stem cells exert therapeutic effects against ischemic stroke via transplantation of exogenous stem cells or stimulation of endogenous stem cells within the neurogenic niches of subventricular zone and subgranular zone, or recruited from the bone marrow through peripheral circulation. In this paper, we review the different sources of stem cells that have been tested in animal models of stroke. In addition, we discuss specific mechanisms of action, in particular neurovascular repair by endothelial progenitor cells, as key translational research for advancing the clinical applications of stem cells for ischemic stroke.
Cerebral ischemia; Cell-based therapies; Vasculature; Blood brain barrier; Endothelial cells
Chronic granulomatous disease (CGD) is a rare genetic disease, which is caused by defects in the NADPH oxidase complex (gp91phox, p22phox, p40phox, p47phox, and p67phox) of phagocytes. This defect results in impaired production of superoxide anions and other reactive oxygen species (ROS), which are necessary for killing bacterial and fungal microorganisms and leads to recurrent, life-threatening bacterial and fungal infections and granulomatous inflammation. The dihydrorhodamine (DHR) flow cytometry assay is a useful diagnostic tool for CGD that can detect absent or reduced NADPH oxidase activity in stimulated phagocytes. We report a patient with X-linked CGD carrying a novel mutation of the CYBB gene whose chimerism status following hematopoietic stem cell transplantation (HSCT) has been rapidly determined using the DHR assay. The level of DHR activity correlates well with short tandem repeat PCR analysis. Considering the advantages of this simple, rapid, and cost-effective procedure, serial measurement of DHR assay would facilitate the rapid determination of a patient's engraftment status, as a supplementary monitoring tool of chimerism status following HSCT.
Chronic granulomatous disease; Dihydrorhodamine assay; Chimerism
Human rhinoviruses (HRVs), in the Enterovirus genus within the family Picornaviridae, are a highly prevalent cause of acute respiratory infection (ARI). Enteroviruses are genetically highly variable, and recombination between serotypes is known to be a major contribution to their diversity. Recently it was reported that recombination events in HRVs cause the diversity of HRV-C. This study analyzed parts of the viral genes spanning the 5′ non- coding region (NCR) through to the viral protein (VP) encoding sequences of 105 HRV field isolates from 51 outpatient cases of Acute Respiratory Infectious Network (ARINET) and 54 inpatient cases of severe lower respiratory infection (SLRI) surveillance, in order to identify recombination in field samples. When analyzing parts of the 5′NCR and VP4/VP2 encoding sequences, we found intra- and interspecies recombinants in field strains of HRV-A and -C. Nineteen cases of recombination events (18.1%) were found among 105 field strains. For HRV-A, there were five cases (4.8%) of intraspecies recombination events and three cases (2.8%) of interspecies recombination events. For HRV-C, there were four cases (3.8%) of intraspecies recombination events and seven cases (6.7%) of interspecies recombination events. Recombination events were significantly more frequently observed in the ARINET samples (18 cases) than in the SLRI samples (1 case; P< 0.0001). The recombination breakpoints were located in nucleotides (nt) 472–554, which comprise stem-loop 5 in the internal ribosomal entry site (IRES), based on the HRV-B 35 sequence (accession no. FJ445187). Our findings regarding genomic recombination in circulating HRV-A and -C strains suggest that recombination might play a role in HRV fitness and could be a possible determinant of disease severity caused by various HRV infections in patients with ARI.
The complete genome sequence of human respiratory syncytial virus genotype A (HRSV-A) with a 72-nucleotide duplication in the C-terminal part of the attachment protein G gene was determined and analyzed. The genome was 15,277 bp in length, and 0.46 to 6.03% variations were identified at the nucleotide level compared with the previously reported complete genome of HRSV-A. Characterization of the genome will improve understanding of the diversity of the HRSV-A major antigens and enable an in-depth analysis of its genetics.
Wharton’s jelly (WJ) is a gelatinous tissue within the umbilical cord that contains myofibroblast-like stromal cells. A unique cell population of WJ that has been suggested as displaying the stemness phenotype is the mesenchymal stromal cells (MSCs). Because MSCs’ stemness and immune properties appear to be more robustly expressed and functional which are more comparable with fetal than adult-derived MSCs, MSCs harvested from the “young” WJ are considered much more proliferative, immunosuppressive, and even therapeutically active stem cells than those isolated from older, adult tissue sources such as the bone marrow or adipose. The present review discusses the phenotypic characteristics, therapeutic applications, and optimization of experimental protocols for WJ-derived stem cells. MSCs derived from WJ display promising transplantable features, including ease of sourcing, in vitro expandability, differentiation abilities, immune-evasion and immune-regulation capacities. Accumulating evidence demonstrates that WJ-derived stem cells possess many potential advantages as transplantable cells for treatment of various diseases (e.g., cancer, chronic liver disease, cardiovascular diseases, nerve, cartilage and tendon injury). Additional studies are warranted to translate the use of WJ-derived stem cells for clinical applications.
umbilical cord; wharton’s jelly; mesenchymal stem cells; phenotypic characteristics; therapeutic applications; experimental protocol
Parkinson’s disease (PD) is a well known neurodegenerative disorder characterized by selective loss of dopaminergic neurons in the substantia nigra pars compact (SN). Although the exact mechanism remains unclear, oxidative stress plays a critical role in the pathogenesis of PD. DJ-1 is a multifunctional protein, a potent antioxidant and chaperone, the loss of function of which is linked to the autosomal recessive early onset of PD. Therefore, we investigated the protective effects of DJ-1 protein against SH-SY5Y cells and in a PD mouse model using a cell permeable Tat-DJ-1 protein. Tat-DJ-1 protein rapidly transduced into the cells and showed a protective effect on 6-hydroxydopamine (6-OHDA)-induced neuronal cell death by reducing the reactive oxygen species (ROS). In addition, we found that Tat-DJ-1 protein protects against dopaminergic neuronal cell death in 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP)-induced PD mouse models. These results suggest that Tat-DJ-1 protein provides a potential therapeutic strategy for against ROS related human diseases including PD.
antioxidant; Parkinson disease; protein transduction; ROS; Tat-DJ-1
Although the number of studies using tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) for the treatment of high-risk pediatric solid tumors has been increasing, documentation of hematologic recovery after tandem HDCT/autoSCT is very limited. For this reason, we retrospectively analyzed the hematologic recovery of 236 children with high-risk solid tumors who underwent tandem HDCT/autoSCT. The median numbers of CD34+ cells transplanted during the first and second HDCT/autoSCT were 4.3 × 106/kg (range 0.6-220.2) and 4.1 × 106/kg (range 0.9-157.6), respectively (P = 0.664). While there was no difference in neutrophil recovery between the first and second HDCT/autoSCT, platelet and RBC recoveries were significantly delayed in the second HDCT/autoSCT (P < 0.001 and P < 0.001, respectively). Delayed recovery in the second HDCT/autoSCT was more prominent when the number of transplanted CD34+ cells was lower, especially if it was < 2 × 106/kg. A lower CD34+ cell count was also associated with increased RBC transfusion requirements and a higher serum ferritin level after tandem HDCT/autoSCT. More CD34+ cells need to be transplanted during the second HDCT/autoSCT in order to achieve the same hematologic recovery as the first HDCT/autoSCT.
High-Dose Chemotherapy; Autologous Stem Cell Transplantation; CD34+ Cells; Hematologic Recovery; Iron Overload
The -D- phenotype is a rare Rh phenotype that strongly expresses D antigen without C, c, E, or e antigens. In -D- phenotype individuals, anti-Rh17 (Hro) is commonly found if there is a history of pregnancy or transfusion with red blood cells (RBCs) that express C, c, E, or e antigens. We report the first case of a -D- phenotype patient with multiple Rh antibodies including anti-Rh17 who had a history of two occasions of transfusion with eight random donor platelet concentrates two and six years ago. We found that a trivial amount of RBCs in the platelet components was able to trigger sensitization to RBC antigens, especially the highly immunogenic and clinically significant Rh antigens, including C, c, E, e or CcEe polypeptides. To avoid unnecessary sensitization and to minimize the risk of hemolytic transfusion reactions in patients with this rare Rh phenotype, a modified strategy for pretransfusion screenings needs to be discussed in the field of transfusion medicine.
Rh-Hr blood group system; Rh isoimmunization; Platelet transfusion
Reactive oxygen species (ROS) contribute to the development of a number of neuronal diseases including ischemia. DJ-1, also known to PARK7, plays an important role in transcriptional regulation, acting as molecular chaperone and antioxidant. In the present study, we investigated whether DJ-1 protein shows a protective effect against oxidative stress-induced neuronal cell death in vitro and in ischemic animal models in vivo. To explore DJ-1 protein's potential role in protecting against ischemic cell death, we constructed cell permeable Tat-DJ-1 fusion proteins. Tat-DJ-1 protein efficiently transduced into neuronal cells in a dose- and time-dependent manner. Transduced Tat-DJ-1 protein increased cell survival against hydrogen peroxide (H2O2) toxicity and also reduced intracellular ROS. In addition, Tat-DJ-1 protein inhibited DNA fragmentation induced by H2O2. Furthermore, in animal models, immunohistochemical analysis revealed that Tat-DJ-1 protein prevented neuronal cell death induced by transient forebrain ischemia in the CA1 region of the hippocampus. These results demonstrate that transduced Tat-DJ-1 protein protects against cell death in vitro and in vivo, suggesting that the transduction of Tat-DJ-1 may be useful as a therapeutic agent for ischemic injuries related to oxidative stress.
brain ischemia; CA1 region, hippocampal; cell survival; neurons; PARK7 protein, human; reactive oxygen species; toxicity
Patients with severe spontaneous cerebellar hemorrhage typically undergo treatment with suboccipital craniectomy and hematoma evacuation. However, this is a stressful procedure for patients due to the long operating time and operation-induced tissue damage. In addition, the durotomy can result in pseudomeningocele. We investigated the efficacy of stereotactic or navigation-guided burr hole aspiration surgery as a treatment for spontaneous hypertensive cerebellar hemorrhage (SHCH).
Between January 2002 and December 2011, 26 patients with SHCH underwent surgery using the stereotactic or navigation-guided burr hole aspiration and catheter insertion technique in our institution.
Mean hematoma volume was 21.8 ± 5.8 cc at admission and 13.1 ± 5.4 cc immediately following surgery. Preoperative Glasgow Coma Scale (GCS) score was 12.5 ± 1.3 and postoperative GCS score was 13.1 ± 1.2. Seven days after surgery, the mean hematoma volume was 4.3 ± 5.6 cc, and there was no occurrence of surgery-related complications during the six-month follow-up period. The mean operation time for catheter insertion was 43.1 ± 8.9 min, and a mean 31.3 ± 6.0 min was also added for extra-ventricular drainage. The mean Glasgow Outcome Scale (GOS) score after six months was 4.6 ± 1.0.
Stereotactic burr hole aspiration surgery for treatment of SHCH is less time-consuming and invasive than other interventions, and resulted in no surgery-related complications. Therefore, we suggest that this surgical method could be a safe and effective treatment option for selected patients with SHCH.
Cerebellar hemorrhage; Aspiration; Stereotactic; Navigation; Outcome
DNA barcoding has been widely used in species identification and biodiversity research. A short fragment of the mitochondrial cytochrome c oxidase subunit I (COI) sequence serves as a DNA bio-barcode. We collected DNA barcodes, based on COI sequences from 156 species (529 sequences) of fish, insects, and shellfish. We present results on phylogenetic relationships to assess biodiversity the in the Korean peninsula. Average GC% contents of the 68 fish species (46.9%), the 59 shellfish species (38.0%), and the 29 insect species (33.2%) are reported. Using the Kimura 2 parameter in all possible pairwise comparisons, the average interspecific distances were compared with the average intraspecific distances in fish (3.22 vs. 0.41), insects (2.06 vs. 0.25), and shellfish (3.58 vs. 0.14). Our results confirm that distance-based DNA barcoding provides sufficient information to identify and delineate fish, insect, and shellfish species by means of all possible pairwise comparisons. These results also confirm that the development of an effective molecular barcode identification system is possible. All DNA barcode sequences collected from our study will be useful for the interpretation of species-level identification and community-level patterns in fish, insects, and shellfish in Korea, although at the species level, the rate of correct identification in a diversified environment might be low.
cytochrome c oxidase subunit I; mitochondrial DNA; molecular taxonomy; taxonomic DNA barcoding
Resveratrol (trans-3,5,4’-trihydroxystilbene) has received considerable attention recently for the potential neuroprotective effects in neurodegenerative disorders where heme oxygenase-1 (HO-1) and sirtuin 1 (SIRT1) represent promising therapeutic targets. Resveratrol has been known to increase HO-1 expression and SIRT1 activity. In this study, the effects of resveratrol and trans-3,5,4’-trimethoxystilbene (TMS), a resveratrol derivative, on cytotoxicity caused by glutamate-induced oxidative stress, HO-1 expression, and SIRT1 activation have been investigated by using murine hippocampal HT22 cells, which have been widely used as an in vitro model for investigating glutamate-induced neurotoxicity. Resveratrol protected HT22 neuronal cells from glutamateinduced cytotoxicity and increased HO-1 expression as well as SIRT1 activity in a concentration-dependent manner. Cytoprotec-tion afforded by resveratrol was partially reversed by the specific inhibition of HO-1 expression by HO-1 small interfering RNA and the nonspecific blockage of HO-1 activity by tin protoporphyrin IX, but not by SIRT1 inhibitors. Surprisingly, TMS, a resveratrol derivative with methoxyl groups in lieu of the hydroxyl groups, and trans-stilbene, a non-hydroxylated analog, failed to protect HT22 cells from glutamate-induced cytotoxicity and to increase HO-1 expression and SIRT1 activity. Taken together, our findings suggest that the cytoprotective effect of resveratrol was at least in part associated with HO-1 expression but not with SIRT1 activation and, importantly, that the presence of hydroxyl groups on the benzene rings of resveratrol appears to be necessary for cytoprotection against glutamate-induced oxidative stress, HO-1 expression, and SIRT1 activation in HT22 neuronal cells.
Resveratrol; trans-3; 5; 4'-Trimethoxystilbene; Heme oxygenase-1; Sirtuin 1; Oxidative stress; Neuroprotection
Sparganum (plerocercoid of Spirometra erinacei) is a parasite that possesses the remarkable ability to survive by successfully modifying its physiology and morphology to suit various hosts and can be found in various tissues, even the nervous system. However, surprisingly little is known about the molecular function of genes that are expressed during the course of the parasite life cycle. To begin to decipher the molecular processes underlying gene function, we constructed a database of expressed sequence tags (ESTs) generated from sparganum.
SpiroESTdb is a web-based information resource that is built upon the annotation and curation of 5,655 ESTs data. SpiroESTdb provides an integrated platform for expressed sequence data, expression dynamics, functional genes, genetic markers including single nucleotide polymorphisms and tandem repeats, gene ontology and KEGG pathway information. Moreover, SpiroESTdb supports easy access to gene pages, such as (i) curation and query forms, (ii) in silico expression profiling and (iii) BLAST search tools. Comprehensive descriptions of the sparganum content of all sequenced data are available, including summary reports. The contents of SpiroESTdb can be viewed and downloaded from the web (http://pathod.cdc.go.kr/spiroestdb).
This integrative web-based database of sequence data, functional annotations and expression profiling data will serve as a useful tool to help understand and expand the characterization of parasitic infections. It can also be used to identify potential industrial drug targets and vaccine candidate genes.
Sparganum; Plerocercoid; Spirometra erinacei; Expressed sequence tags (ESTs); Database
NF-κB is a multifunctional transcription factor involved in diverse biological processes. It has been well documented that NF-κB can be activated in response to various stimuli. While signal-inducible NF-κB activation mechanisms have been extensively characterized, exogenous signal-independent intrinsic NF-κB activation processes remain poorly understood. Here we show that IκB kinase β (IKKβ) can be intrinsically activated in the nucleus by a homeobox protein termed Nkx3.2 in the absence of exogenous IKK-activating signals. We found that ubiquitin chain-dependent, but persistent, interactions between Nkx3.2 and NEMO (also known as IKKγ) can give rise to constitutive IKKβ activation in the nucleus. Once the Nkx3.2-NEMO-IKKβ complex is formed in the nucleus, IKKβ-induced Nkx3.2 phosphorylation at Ser148 and Ser168 allows βTrCP to be engaged to cause IκB-α ubiquitination independent of IκB-α phosphorylation at Ser32 and Ser36. Taken together, our results provide a novel molecular explanation as to how an intracellular factor such as Nkx3.2 can accomplish persistent nuclear IKK activation to enable intrinsic and constitutive degradation of IκB in the nucleus in the absence of exogenous NF-κB-activating signals, which, in turn, plays a role in chondrocyte viability maintenance.