tbuckley/cabot-search huggingface dataset:
Publication and reporting of clinical trial results: cross sectional analysis across academic medical centers
Authors: Ruijun Chen, Nihar R Desai, Joseph S Ross, Weiwei Zhang, Katherine H Chau, Brian Wayda, Karthik Murugiah, Daniel Y Lu, Amit Mittal, Harlan M Krumholz
Journal: BMJ (2016)

<b>Objective</b>&nbsp;To determine rates of publication and reporting of results within two years for all completed clinical trials registered in ClinicalTrials.gov across leading academic medical centers in the United States. <b>Design</b>&nbsp;Cross sectional analysis. <b>Setting</b>&nbsp;Academic medical centers in the United States. <b>Participants</b>&nbsp;Academic medical centers with 40 or more completed interventional trials registered on ClinicalTrials.gov. <b>Methods</b>&nbsp;Using the Aggregate Analysis of ClinicalTrials.gov database and manual review, we identified all interventional clinical trials registered on ClinicalTrials.gov with a primary completion date between October 2007 and September 2010 and with a lead investigator affiliated with an academic medical center. <b>Main outcome measures</b>&nbsp;The proportion of trials that disseminated results, defined as publication or reporting of results on ClinicalTrials.gov, overall and within 24 months of study completion. <b>Results</b>&nbsp;We identified 4347 interventional clinical trials across 51 academic medical centers. Among the trials, 1005 (23%) enrolled more than 100 patients, 1216 (28%) were double blind, and 2169 (50%) were phase II through IV. Overall, academic medical centers disseminated results for 2892 (66%) trials, with 1560 (35.9%) achieving this within 24 months of study completion. The proportion of clinical trials with results disseminated within 24 months of study completion ranged from 16.2% (6/37) to 55.3% (57/103) across academic medical centers. The proportion of clinical trials published within 24 months of study completion ranged from 10.8% (4/37) to 40.3% (31/77) across academic medical centers, whereas results reporting on ClinicalTrials.gov ranged from 1.6% (2/122) to 40.7% (72/177). <b>Conclusions</b>&nbsp;Despite the ethical mandate and expressed values and mission of academic institutions, there is poor performance and noticeable variation in the dissemination of clinical trial results across leading academic medical centers.
A phase I/II dose-escalation trial of EPO906 every 3 weeks in patients with relapsed/refractory ovarian, primary fallopian, or primary peritoneal cancer
Authors: W. M. Smit, A. H. Honkoop, S. Spanik, M. Wagnerova, W. W. T. B. Huinink, A. M. Oza, S. B. Kaye, R. Mull, R. Pereno, I. Sklenar
Journal: Journal of Clinical Oncology (2004)

5102 Background: Patients (pts) with newly diagnosed advanced ovarian cancer generally receive a taxane in combination with a platinum agent. However, pts refractory to this therapy have few treatment options. Taxane efficacy can be limited by the development of drug-resistance mechanisms, and taxanes are associated with neutropenia and neuropathies. EPO906 is a potent microtubule stabilizer that has demonstrated clinical cytotoxic activity in taxane-sensitive, -resistant, and -refractory tumors. In a phase I/II study, we investigated the safety and efficacy of EPO906 in pts with advanced ovarian, primary fallopian, or primary peritoneal cancer who had failed to respond to or had relapsed within 6 months of first-line taxane plus platinum therapy. Methods: During phase I, dose escalation followed the standard 3 + 3 design until the MTD was reached. Pts received EPO906 at a starting dose of 6.5 mg/m2 via 5-min IV infusion once every 3 wks with aggressive diarrhea management at first sign of abdominal cramping. During phase II, pts will be treated at the MTD for 6 cycles or until disease progression. Results: To date, 6 pts have been enrolled in 2 cohorts receiving 6.5 mg/m2 (n = 3) or 7.0 mg/m2 (n = 3) EPO906. Median age was 56 yrs (range, 33 - 69 yrs). Before study entry, these pts had received a median of 6 cycles of carboplatin plus paclitaxel. Pts have received a median of 3 cycles (range, 2 - 6 cycles) of EPO906. No DLTs have been reported; thus, the MTD has not been reached. Grade 3 AEs—vomiting (n = 2), diarrhea (n = 1), and dehydration (n = 1)—were observed in cycle 2 and thus were not DLT. Grade ≤ 2 diarrhea (n = 2) and nausea (n = 1) were also reported. No pts experienced hematologic or peripheral neurologic toxicity. Radiologic tumor assessment shows 2 pts with SD (1 at 4 cycles; 1 at 6 cycles). Conclusion: Preliminary data indicate that EPO906 administered once every 3 wks is safe and well tolerated in this population. MTD has not been reached and dose escalation continues. Phase II portion of this study will assess the clinical activity of EPO906 in the treatment of advanced ovarian, primary fallopian, or primary peritoneal cancer. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Pharma AG Novartis Pharma AG Novartis Pharma AG Novartis Pharma AG; Novartis Pharmaceuticals, Inc. Novartis Pharmaceuticals, Inc.
Abstract 334: Proliferation of Cardiomyocytes from a Rat Model of Heart Hypoplasia
Authors: Corin Williams, Raymond Wang, Lauren D Black
Journal: Circulation Research (2014)

Decreased cardiomyocyte proliferation has been implicated in underdevelopment of the left ventricle in Hypoplastic Left Heart Syndrome (HLHS). However, it is not clear if cardiomyocytes in HLHS have an inherent defect that inhibits proliferation or if it is the result of abnormal external cues (eg, alterations to mechanical loading or extracellular matrix). We hypothesized that cardiomyocytes from hypoplastic hearts would be capable of proliferation if removed from the unhealthy cardiac environment. We used the rat model of congenital diaphragmatic hernia (CDH) via nitrofen treatment in the pregnant dam at E10 to induce heart hypoplasia in the developing fetuses; control dams were gavaged with olive oil only. Fetuses were harvested at E21 and the presence of CDH was determined. CDH+ hearts were smaller and abnormally shaped compared to healthy controls ( Fig. 1A ). Ki67 staining revealed that CDH+ hearts had significantly lower cell proliferation vs. healthy hearts ( Fig. 1B ). However, when cells were placed in culture, CDH+ cardiomyocytes expanded more rapidly compared to control cardiomyocytes ( Fig. 1C ). CDH+ cells also had smaller, more disorganized sarcomeres (not shown) and decreased expression of cardiac genes compared to controls ( Fig. 1D ), suggesting that CDH+ cells were less mature. Our findings suggest that cardiomyocytes from hypoplastic hearts may be arrested in an immature state but are not necessarily defective, and have potential for proliferation and growth. Strategies that aim to increase cardiomyocyte proliferation during development in HLHS may be a novel strategy to encourage left ventricular growth and lead to better outcomes in these patients.
Use of systematic analysis of DNA repair pathways in head and neck cancer (HNC) to identify XPF as a novel predictor of induction response, and pMK2 relationship to chemoradiotherapy
Authors: T. Y. Seiwert, E. E. Cohen, X. Wang, M. Kocherginsky, M. Bhayani, K. Stenson, S. Finn, E. M. O'Regan, D. Weaver, E. E. Vokes
Journal: Journal of Clinical Oncology (2008)

6003 Background: Radiotherapy and most chemotherapeutic agents damage DNA and lack of adequate repair induces tumor cell death. Recently analysis of the nucleotide excision repair pathway identified ERCC1 as a predictor for platinating agents in multiple tumors. There are 6 DNA repair pathways which interrelate. We performed a more comprehensive analysis to identify clinically promising DNA repair biomarkers. Methods: 73 FFPE tumor samples from locally advanced HNC pts treated with carboplatin/taxane induction (I) followed by FHX-based chemoradiotherapy (CRT) were analyzed. IHC staining for 8 DNA repair biomarkers (5 pathways) was performed (ERCC1 (clone 8F1), XPF, pMK2, PARP, PAR1, pH2AX, MLH1, FANCD2), as well as relevant associated markers Ki67 (proliferation), EGFRvIII (truncated EGFR), p16 (HPV screen). IHC was analyzed by automated image processing, and 2 pathologists (blinded). Scores for nuclear/cytoplasmic intensity/quantity(IxQ) were correlated with response/survival. Immunoblot analysis in cell lines was done to determine antibody specificity. Further staining of 50pts (I+CRT) and 40pts (CRT) is ongoing. Results: Low levels of XPF were associated with response to induction chemotherapy (p=0.039). In contrast ERCC1 was marginally related to overall survival (p=0.085) and in our set did not correlate with response (p=0.41). pMK2 did not correlate with induction at all (p=0.74), but correlated with overall survival (p=0.026) suggesting that pMK2 may relate to CRT. EGFRvIII was positive in 48% of HNC. XPF, ERCC1, and MLH1 stained adjoining normal parabasal zones, whereas FANCD2 stained the suprabasal layer. An unsupervised cluster analysis suggests that ERCC1 and pMK2 associate. Immunoblot analysis of HNC tumor cell lines demonstrated multiple non-ERCC1 bands for the 8F1 antibody, suggesting limited specificity. Conclusion: XPF is a novel predictor of response to induction chemotherapy, which in our study worked better than ERCC1. pMK2 differentiated a subgroup with improved survival potentially related to CRT. Further study of pMK2 is needed and analysis of a CRT only cohort is ongoing. Analysis of multiple DNA repair markers holds promise. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration DNAR DNAR
EEG-based neurocinematics: challenges and prospects
Authors: Ho-Seung Cha, Won-Du Chang, Young Seok Shin, Dong Pyo Jang, Chang-Hwan Im
Journal: Brain-Computer Interfaces (2015)

Neurocinematics is an emerging research discipline that studies audiences' cognitive and affective responses to cinematic stimuli. To date, functional magnetic resonance imaging (fMRI) has been the most widely used research tool for neurocinematics studies; however, recent studies have shown that electroencephalography (EEG) can also be a promising tool for neurocinematics studies thanks to its excellent temporal resolution. In this article, after discussing challenges and prospects for EEG-based neurocinematics, we introduced two potential film-rating indices named 'empathy index' and 'reactivity index' as examples of EEG-based neurocinematic markers. Preliminary experiments showed that the new indices have the potential to be used as promising tools for film evaluation.
Dextran-b-poly(lactide-co-glycolide) polymersome for oral delivery of insulin: In vitro and in vivo evaluation
Authors: Mona Alibolandi, Fatemeh Alabdollah, Fatemeh Sadeghi, Marzieh Mohammadi, Khalil Abnous, Mohammad Ramezani, Farzin Hadizadeh
Journal: Journal of Controlled Release (2016)
Increased humoral and cellular immunity in patients (pts) with advanced melanoma treated with ipilimumab
Authors: S. Parker, D. Berman, K. L. Bennett, S. Alaparthy, Z. Tsuchihashi, S. D. Chasalow, P. Zhan
Journal: Journal of Clinical Oncology (2009)

3031 Background: Ipilimumab is an anti-CTLA-4 monoclonal antibody (Ab) that overcomes T-cell suppression. In this phase II study (CA184004), humoral and cellular responses were assessed in ipilimumab-treated pts with unresectable stage III/IV melanoma. Methods: Ipilimumab 3 or 10 mg/kg was given every 3 weeks x 4. Tetanus boosters were given ≤10 days pre-treatment. Influenza and pneumococcal vaccines were given 5 days after first ipilimumab dose. Tetanus, anti-influenza, and anti-pneumococcal Ab levels were assessed at pre-dose and Wk 7. Humoral response to 5 tumor antigens (Ag) and a control Ag (DHFR) were examined at baseline (BL) and at Wks 4, 8–9, and 12. DTH skin tests were given at pre-dose and Wk 4, with responses recorded 15 minutes (min) and 24–72 hours (hrs) post-test. Peripheral T-cell populations were evaluated through flow cytometry at BL, Wk 4, and Wk 12. Results: Pts received ipilimumab 3 (n = 40) or 10 mg/kg (n = 42). Increases from BL in humoral responses to pneumococcal (40–50/78 pts, depending on Ab) and tetanus (58/78 pts) vaccines were noted, even in pts who did not receive on-study pneumococcal (4–9 pts) or tetanus (7 pts) vaccines. Increased humoral response to influenza only occurred in pts receiving the influenza vaccine. Maximum increase from BL of ≥ 5-fold titer (clinically meaningful threshold) in humoral response to tumor Ag MELANA (23.2% of pts), SSX2 (20.3%), NYES01 (18.8%), MAGEA4 (10.1%), and P53 (4.3%) (DHFR, 4.3%) was noted without tumor vaccines. Tumor Ag response was not associated with clinical activity (complete or partial response, or stable disease ≥ 24 wks). Increased DTH reactions were noted for tetanus, 24–72 hrs (3 mg/kg: 5/7 pts; 10 mg/kg: 3/6 pts); tuberculin, 15 min (3 mg/kg: 7/15 pts; 10 mg/kg: 4/15 pts); Candida, 15 min (3 mg/kg: 4/6 pts; 10 mg/kg: 2/7 pts); and Trichophyton, 15 min (3 mg/kg: 3/4 pts; 10 mg/kg: 2/5 pts). Significant increases from BL in percents of HLA-DR+ CD4+ (p = 9.3x10 -7 ), HLA-DR+ CD8+ (p = 0.018), and ICOS+ CD4+ (p = 0.0027) effector T cells were noted. Conclusions: Humoral immunity in ipilimumab-treated pts increased (± vaccination) in an Ag-dependent manner and cellular immunity was enhanced. Change in tumor Ag response was not associated with clinical activity. [Table: see text]
Exploiting evolutionary principles to prolong tumor control in preclinical models of breast cancer
Authors: Pedro M. Enriquez-Navas, Yoonseok Kam, Tuhin Das, Sabrina Hassan, Ariosto Silva, Parastou Foroutan, Epifanio Ruiz, Gary Martinez, Susan Minton, Robert J. Gillies, Robert A. Gatenby
Journal: Science Translational Medicine (2016)

Using evolutionary principles to guide drug administration, monotherapy with paclitaxel can maintain prolonged stability of breast cancer in preclinical models.
Modulation of irinotecan (Ir) efficacy with capecitabine (Cp): Albert Einstein and Montefiore Cancer Center experience
Authors: S. Karri, M. Macapinlac, B. Kiner-Strachan, G. L. Goldberg, A. Kaubisch, F. J. Camacho, I. Chaudhry, D. Verdier-Pinard, S. Mani, S. Goel
Journal: Journal of Clinical Oncology (2005)

2072 Background: We have previously demonstrated that Cp may be administered safely as a daily “flat” total dose with Ir given every 3 weeks [Am J Clin Oncol 2002 25: 528–34]. Since the usual North American schedule of Ir is a weekly dosing scheme, we designed a study using a weekly combined drug regimen. Methods: This is an open label standard phase I dose escalation trial. Ir was given as a 30-minute infusion on days 1 and 8, without prophylactic atropine, and Cp on days 1–14 of a 21day cycle. Results: Forty seven patients (pt) -median age 60 (range 32–83) years; performance status 0–1 (96%); diagnoses- ovarian (10), breast (5), cervical (5), colorectal (10) and others (17) have received 202 (1–18) cycles in 6 dose cohorts-Ir (mg/m2)/Cp (mg/m2/day in 2 divided doses) 75/1500, 85/1500, 85/1750, 100/1750, 100/2000, 115/2000. There was no cycle 1 dose limiting toxicity (DLT) in the first four dose cohorts tested. At the highest dose level (Ir/Cp 115/2000), 1 of 3 pt developed grade 4 neutropenia with fatal gram-negative sepsis. At dose level 5 (Ir/Cp 100/2000), 2 of 21 evaluable patients developed cycle 1 DLT - grade 3 diarrhea/vomiting and grade 3 diarrhea. Overall, across all doses and patients, the grade 3–4 toxicities observed were diarrhea (12 pt), vomiting (2 pt), fatigue (5 pt), hand-foot syndrome (1 pt), neutropenia (6 pt), anemia (4 pt), thrombocytopenia (2 pt) and elevation of AST and ALT (1 pt). Acute toxicities observed within hours of Ir included the cholinergic syndrome in 4 patients that resolved with, and did not recur in subsequent infusions with prophylactic atropine. Anti-tumor responses include partial response in 8 of 35 evaluable (23%) pts (2 breast, 4 ovarian, 1 prostate, 1 cervical), a minimal response (1 pt- breast), stable disease in 16 pt (44%) and a decrease in CA-125 (1 pt-ACUP). Conclusions: The combination of Ir and Cp is safe and well tolerated at a dose of 100 mg/m2and 2000 mg/m2/d, respectively. There is moderate anti-tumor activity in heavily treated and chemotherapy refractory patients. This combination warrants further evaluation in breast, cervical, and ovarian cancer and other solid tumors. We are currently evaluating the pharmacokinetic effects of Cp on the disposition of Ir. No significant financial relationships to disclose.
Phase I study to evaluate the safety and efficacy of sunitinib in combination with FOLFIRI in treatment-naïve metastatic colorectal cancer (mCRC)
Authors: N. Starling, F. Vázquez, D. Cunningham, I. Chau, F. J. Ramos, M. P. Saunders, T. J. Iveson, L. Verkh, J. Tursi, A. Carrato
Journal: Journal of Clinical Oncology (2008)

3563 Background: Sunitinib malate (SU) is an oral, multitargeted inhibitor of VEGFR, PDGFR, KIT, RET and FLT3, approved in advanced RCC and imatinib-resistant/-intolerant GIST. VEGF and VEGFRs are expressed in CRC and correlate with increased angiogenesis. Angiogenesis inhibition by SU may augment antitumor activity when combined with chemotherapy regimens, e.g. FOLFIRI. Methods: Successive cohorts of 3–6 treatment-naïve mCRC patients (pts) received FOLFIRI (irinotecan 180 mg/m2, leucovorin 200 mg/m2 and 5-FU 400 mg/m2 on day 1, followed by 5-FU 2,400 mg/m2 46-hr infusion) every 2 wks with SU 37.5 or 50 mg/d on a 4/2 schedule (4 wks on, 2 wks off) or SU 37.5 or 25 mg/d on a continuous dosing schedule. The primary endpoint was the MTD, the dose at which ≤1 in 6 pts had DLTs, and overall safety of FOLFIRI + SU. PK and antitumor activity (RECIST) were also assessed. Results: By Dec 2007, 27 pts on the SU 4/2 schedule (21 at 37.5; 6 at 50 mg/d) were safety- evaluable. No DLTs were seen in the first 6 pts at 37.5 mg/d; 2 DLTs were seen in the expansion cohort (n=15) (both febrile neutropenia, one with suspected line infection). 2 pts at 50 mg/d had DLTs (febrile neutropenia and gr 4 neutropenia). 8 pts receiving SU continuously (3 at 37.5; 5 at 25 mg/d) were safety-evaluable. 2 pts at each dose had a DLT (37.5 mg/d, gr 4 neutropenia and DVT; 25 mg/d, both gr 4 neutropenia). The MTD for SU on the 4/2 schedule with FOLFIRI was 37.5mg/d. The 25 mg/d continuous dosing regimen + FOLFIRI was not tolerable. Dose delays (mainly for hematologic recovery) of ≥1 week were most common in the SU 50 mg/d 4/2 group (21% of all FOLFIRI cycles). Updated tolerability data will be presented. There were no clinically significant changes in PK parameters. Initial efficacy data are shown (Table). Conclusions: The MTD of SU combined with FOLFIRI is 37.5mg/d on a 4/2 schedule. This regimen is tolerable and has promising antitumour activity in treatment-naïve mCRC pts. A phase III study is enrolling pts to further evaluate this regimen in mCRC. mg/d 4/2 Continuous 37.5 n=21 50 n=6 37.5 n=3 25 n=7 Confirmed PR 8 0 0 2 SD 10 6 3 2 PD 1 0 0 0 Unevaluable 2 - - 3 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Merck, Pfizer, Roche, sanofi-aventis Merck, Pfizer, Roche, sanofi-aventis Pfizer Pfizer
Abstract 15568: Selective Deletion of Smad4 in Smooth Muscle Cells Causes Thoracic Aortic Aneurysm in Mice
Authors: Daniela Carnevale, Raimondo Carnevale, Francesco Da Ros, Giuseppe Cifelli, Dario Bizzotto, Paola Braghetta, Giorgio Bressan, Giuseppe Lembo
Journal: Circulation (2015)

TGFβ signaling have been implicated in the onset of thoracic aortic aneurysms (TAAs). Recently, it has been described that mutations in SMAD4, an intracellular transducer required in the TGFβ canonical pathway, present aortic disease in humans. Although transgenic models recapitulating mutations of TGFβ pathway have been studied, the role of Smad4 in the onset of TAA has never been explored. Smad4 homozygotes mice are embryonically lethal, thus, we postnatally targeted the gene, using a tamoxifen (TAM)-inducible Cre recombinase under the smooth muscle myosin heavy chain promoter. Activation by TAM suppressed Smad4 in aorta SMCs of Smadf/f;Myh11-CreERT2 mice. Most of these mice died 4/6 months later from hemothorax due to rupture of thoracic aorta, while untreated animals survived. Echocardiography showed a progressive dilatation of aorta and TAA formation. Histological analysis revealed progressive fragmentation of elastic lamellae with increased inflammatory infiltrates at sites of disarrangement, rich in macrophages. At the molecular level, we found that lack of Smad4 was followed by increased levels of P-Smad2 and P-Smad1/5/8 early after TAM. This finding suggested an enhancement of TGFβ receptors activity, a condition that could increase non-canonical TGFβ signaling, the canonical one being certainly depressed. We actually found a significant increase in one of the non-canonical TGFβ signaling, i.e. the p65 subunit of NFkB, a protein complex involved in regulating responses to different stress stimuli, including cytokines. Given the particular relevance that the latter molecules may have in TAA, we tested expression of some of them, finding a selective IL-1β upregulation, produced and stored as an inactive precursor and released in its active form by caspase-1 cleavage. In turn, caspase-1 requires the function of NLRP3 inflammasome, a multiprotein platform that assembles in response to infection and tissue damage and is responsible for activation of inflammatory caspases. Therefore, we also tested NLRP3 mRNA levels and found them to be significantly upregulated. Overall, we demonstrated that selective Smad4 deletion in the SMC of adult mice is sufficient to induce ultrastructural damage and immune reaction culminating in the onset of TAA.
Pleiotropic roles of metallothioneins as regulators of chondrocyte apoptosis and catabolic and anabolic pathways during osteoarthritis pathogenesis
Authors: Yoonkyung Won, Youngnim Shin, Churl-Hong Chun, Yongsik Cho, Chul-Won Ha, Jin-Hong Kim, Jang-Soo Chun
Journal: Annals of the Rheumatic Diseases (2016)

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.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).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.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.