Biomimetic Bone-Like Composite Hydrogel Scaffolds Composed of Collagen Fibrils and Natural Hydroxyapatite for Promoting Bone Repair.

Bone is a complex organic-inorganic composite tissue composed of ∼30% organics and ∼70% hydroxyapatite (HAp). Inspired by this, we used 30% collagen and 70% HAp extracted from natural bone using the calcination method to generate a biomimetic bone composite hydrogel scaffold (BBCHS). In one respect, BBCHS, with a fixed proportion of inorganic and organic components similar to natural bone, exhibits good physical properties. In another respect, the highly biologically active and biocompatible HAp from natural bone effectively promotes osteogenic differentiation, and type I collagen facilitates cell adhesion and spreading. Additionally, the well-structured porosity of the BBCHS provides sufficient growth space for bone marrow mesenchymal stem cells (BMSCs) while promoting substance exchange. Compared to the control group, the new bone surface of the defective location in the B-HA70+Col group is increased by 3.4-fold after 8 weeks of in vivo experiments. This strategy enables the BBCHS to closely imitate the chemical makeup and physical structure of natural bone. With its robust biocompatibility and osteogenic activity, the BBCHS can be easily adapted for a wide range of bone repair applications and offers promising potential for future research and development.

Small needle-knife versus extracorporeal shock wave therapy for the treatment of plantar fasciitis: A systematic review and meta-analysis.

Background: Plantar fasciitis (PF) is the most common cause of chronic heel pain among adults. Extracorporeal shock wave therapy (ESWT) is the recommended in the current guidelines, and the small needle-knife yields acceptable clinical effects for musculoskeletal pain. Objective: To systematically compare the efficacy of the small needle-knife versus ESWT for the treatment of PF. Methods: The present review was registered in the International Prospective Register of Systematic Reviews (i.e., "PROSPERO", CRD42023448813). Two of the authors searched electronic databases for randomized controlled trials (RCTs) comparing the small needle-knife versus ESWT for the treatment of PF, and collected outcomes including curative effect, pain intensity, and function. Risk of bias was assessed using the Cochrane Handbook Risk of Bias tool and the quality of the RCTs was evaluated according to the Jadad Scale. The same authors independently performed data extraction from the included studies, which were imported into Review Manager version 5.4.1(Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2020) for meta-analysis. Results: The initial literature search retrieved 886 studies, of which 6 were eventually included in this study. Meta-analysis revealed no significant difference in curative effect (OR = 1.87; 95 % CI [0.80, 4.37], p = .15) nor short-term pain improvement (MD = 2.20; 95 % CI [-2.77, 7.16], p = .39) between the small needle-knife and ESWT. However, the small needle-knife may be more effective than ESWT for pain improvement in mid-term (MD = 9.11; 95 % CI [5.08, 13.15], p＜ .00001) and long-term follow-ups (MD = 10.71; 95 % CI [2.18, 19.25], p＜ .00001). Subgroup analysis revealed that the small needle-knife combined with a corticosteroid injection yielded a statistically significant difference in reduction of pain intensity at all follow-ups (MD = 4.84; 95 % CI [1.33, 8.36], p = .007; MD = 10.99; 95 % CI [8.30, 13.69], p＜ .00001; MD = 17.87; 95 % CI [15.26, 20.48], p＜ .00001). Meta-analysis revealed no statistical differences in short-term (MD = 1.34; 95 % CI [-3.19, 5.86], p = .56) and mid-term (MD = 2.75; 95 % CI [-1.21, 6.72], p = . 17) functional improvement between the needle-knife and ESWT groups. In a subgroup analysis of moderate-quality studies, the small needle-knife demonstrated a favorable effect on mid-term functional improvement (MD = 1.58; 95 % CI [0.52, 2.65], p = .004), with low heterogeneity (χ2 = 0.77, p = .038, I2 = 0 %). Conclusion: Pain reduction and functional improvement are essential for the treatment of PF. Therefore, treatment using the small needle-knife may be superior to ESWT. Results of this systematic review and meta-analysis may provide alternative treatment options for patients with PF as well as more reliable, evidence-based recommendations supporting use of the small needle-knife.

CircGNB1 drives osteoarthritis pathogenesis by inducing oxidative stress in chondrocytes.

BACKGROUND: Circular RNAs (circRNAs) have risen to prominence as important regulators of biological processes. This study investigated whether circGNB1 functions as a competitive endogenous RNA to regulate the pathological process of oxidative stress in age-related osteoarthritis (OA). METHODS: The relationship between circGNB1 expression and oxidative stress/OA severity was determined in cartilages from OA patients at different ages. The biological roles of circGNB1 in oxidative stress and OA progression, and its downstream targets were determined using gain- and loss-of-function experiments in various biochemical assays in human chondrocytes (HCs). The in vivo effects of circGNB1 overexpression and knockdown were also determined using a destabilization of the medial meniscus (DMM) mouse model. RESULTS: Increased circGNB1 expression was detected in HCs under oxidative and inflammatory stress and in the cartilage of older individuals. Mechanistically, circGNB1 sponged miR-152-3p and thus blocked its interaction with its downstream mRNA target, ring finger protein 219 (RNF219), which in turn stabilized caveolin-1 (CAV1) by preventing its ubiquitination at the K47 residue. CircGNB1 inhibited IL-10 signalling by antagonizing miR-152-3p-mediated RNF219 and CAV1 inhibition. Consequently, circGNB1 overexpression promoted OA progression by enhancing catabolic factor expression and oxidative stress and by suppressing anabolic genes in vitro and in vivo. Furthermore, circGNB1 knockdown alleviated the severity of OA, whereas circGNB1 overexpression had the opposite effect in a DMM mouse model of OA. CONCLUSION: CircGNB1 regulated oxidative stress and OA progression via the miR-152-3p/RNF219/CAV1 axis. Modulating circGNB1 could be an effective strategy for treating OA.

An inducible long noncoding RNA, LncZFHX2, facilitates DNA repair to mediate osteoarthritis pathology.

Cartilage homeostasis is essential for chondrocytes to maintain proper phenotype and metabolism. Because adult articular cartilage is avascular, chondrocytes must survive in low oxygen conditions, and changing oxygen tension can significantly affect metabolism and proteoglycan synthesis in these cells. However, whether long noncoding RNA participate in cartilage homeostasis under hypoxia has not been reported yet. Here, we first identified LncZFHX2 as a lncRNA upregulated under physiological hypoxia in cartilage, specifically by HIF-1α. LncZFHX2 knockdown simultaneously accelerated cellular senescence, targeted multiple components of extracellular matrix metabolism, and increased DNA damage in chondrocytes. Through a series of in vitro and in vivo experiments, we identified that LncZFHX2 performed a novel function that regulated RIF1 expression through forming a transcription complex with KLF4 and promoting chondrocyte DNA repair. Moreover, chondrocyte-conditional knockout of LncZFHX2 accelerated injury-induced cartilage degeneration in vivo. In conclusion, we identified a hypoxia-activated DNA repair pathway that maintains matrix homeostasis in osteoarthritis cartilage.

CircFNDC3B regulates osteoarthritis and oxidative stress by targeting miR-525-5p/HO-1 axis.

Osteoarthritis (OA) is a common chronic degenerative joint disease associated with a variety of risk factors including aging, genetics, obesity, and mechanical disturbance. This study aimed to elucidate the function of a newly discovered circular RNA (circRNA), circFNDC3B, in OA progression and its relationship with the NF-κB signaling pathway and oxidative stress. The circFNDC3B/miR-525-5p/HO-1 axis and its relationship with the NF-κB signaling pathway and oxidative stress were investigated and validated using fluorescence in situ hybridization, real-time PCR, western blotting, immunofluorescence analysis, luciferase reporter assays, pull-down assays, and reactive oxygen species analyses. The functions of circFNDC3B in OA was investigated in vitro and in vivo. These evaluations demonstrated that circFNDC3B promotes chondrocyte proliferation and protects the extracellular matrix (ECM) from degradation. We also revealed that circFNDC3B defends against oxidative stress in OA by regulating the circFNDC3B/miR-525-5p/HO-1 axis and the NF-κB signaling pathway. Further, we found that overexpression of circFNDC3B alleviated OA in a rabbit model. In summary, we identified a new circFNDC3B/miR-525-5p/HO-1 signaling pathway that may act to relieve OA by alleviating oxidative stress and regulating the NF-κB pathway, resulting in the protection of the ECM in human chondrocytes, highlighting it as a potential therapeutic target for the treatment of OA.

The Influence of Endplate Morphology on Cage Subsidence in Patients With Stand-Alone Oblique Lateral Lumbar Interbody Fusion (OLIF).

STUDY DESIGN: A retrospective study of prospectively collected radiographic and clinical data. OBJECTIVE: This study aims to investigate the relationship between endplate morphology parameters and the incidence of cage subsidence in patients with mini-open single-level oblique lateral lumbar interbody fusion (OLIF). METHODS: We included 119 inpatients who underwent OLIF from February 2015 to December 2017. A total of 119 patients with single treatment level of OLIF were included. Plain anteroposterior and lateral radiograph were taken preoperatively, postoperatively, and during follow-up. The correlation between disc height, endplate concave angle/depth, cage position and cage subsidence were investigated. Functional rating index (Visual Analogue Scale for pain, and Roland Morris Disability Questionnaire) were employed to assess clinical outcomes. RESULTS: Cage subsidence was more commonly seen at the superior endplates (42/119, 35.29%) than at the inferior endplates (6/119, 5.04%) (p < 0.01). More importantly, cage subsidence was significantly less in patients with superior endplates that were without concave angle (3/20, 15%) than with concave angle (37/99, 37.37%) (p < 0.05). Cage subsidence correlated negatively with preoperative anterior disc height (r = -0.21, p < 0.05), but positively with disc distraction rate (r = 0.27, p < 0.01). Lastly, the distance of cage to the anterior edges of the vertebral body showed a positive correlation (r = 0.26, p < 0.01). CONCLUSIONS: This study for the first time demonstrated that endplate morphology correlates with cage subsidence after OLIF. Since relatively flat endplates with smaller concave angle significantly diminish the incidence of subsidence, the morphology of cage surface should be taken into consideration when designing the next generation of cage. In addition, precise measurement of the disc height to avoid over-distraction, and more anteriorly placement of the cage is suggested to reduce subsidence.

Correlation Analysis Between Basic Diseases and Subsequent Vertebral Fractures After Percutaneous Kyphoplasty (PKP) for Osteoporotic Vertebral Compression Fractures.

BACKGROUND: Percutaneous kyphoplasty (PKP) is a widely accepted surgical treatment modality for painful osteoporotic vertebral compression fractures. The risk factors cause of subsequent vertebral fractures after PKP are debated. OBJECTIVES: To evaluate risk factors for the occurrence of new vertebral compression fractures after PKP. STUDY DESIGN: A retrospective study. SETTING: A single-center inpatient population. METHODS: A total of 921 patients (1,152 vertebrae) with PKP were investigated. Among those patients, 111 patients (155 levels) incurred refractures after PKP. RESULTS: The average bone mineral density was -3.27 in the "refracture"group and -3.00 in the "no fracture" group (P = 0.031). Morbidities of women were significantly higher in the "refracture" group (90.99%) compared with the "no fracture" group (81.73%) (P = 0.015). Among the basic diseases, several diseases (history of previously fracture, previously osteoporosis, gallstone disease, stomach disease, and ovariectomy) are associated with refractures after PKP (P < 0.05). And antiosteoporotic treatment (calcium + vitamin D or zoledronate) after PKP can also significantly reduce the occurrence of refracture (P < 0.000). In addition, logistic regression analysis also showed that most of the above contents had significant correlation with the refracture after PKP (P < 0.05), except for gallstone disease (P = 0.362). LIMITATIONS: Retrospective study, single center. CONCLUSION: Osteoporosis is the main cause of refracture after PKP. Elderly women were found to be more susceptible than elderly men to refracture. Patients with a history of previously fracture, previously osteoporosis, stomach ulcer, and ovariectomy are more likely to be refracture. Antiosteoporosis treatment (calcium + vitamin D or zoledronate) after PKP can reduce the risk of refracture.

CircSLC7A2 protects against osteoarthritis through inhibition of the miR-4498/TIMP3 axis.

OBJECTIVES: Circular RNAs (circRNAs) are noncoding RNAs that compete against other endogenous RNA species, such as microRNAs, and have been implicated in many diseases. In this study, we investigated the role of a new circRNA (circSLC7A2) in osteoarthritis (OA). MATERIALS AND METHODS: The relative expression of circSLC7A2 was significantly lower in OA tissues than it was in matched controls, as shown by real-time quantitative polymerase chain reaction (RT-qPCR). Western blotting, RT-qPCR and immunofluorescence experiments were employed to evaluate the roles of circSLC7A2, miR-4498 and TIMP3. The in vivo role and mechanism of circSLC7A2 were also conformed in a mouse model. RESULTS: circSLC7A2 was decreased in OA model and the circularization of circSLC7A2 was regulated by FUS. Loss of circSLC7A2 reduced the sponge of miR-4498 and further inhibited the expression of TIMP3, subsequently leading to an inflammatory response. We further determined that miR-4498 inhibitor reversed circSLC7A2-knockdown-induced OA phenotypes. Intra-articular injection of circSLC7A2 alleviated in vivo OA progression in a mouse model of anterior cruciate ligament transection (ACLT). CONCLUSIONS: The circSLC7A2/miR-4498/TIMP3 axis of chondrocytes catabolism and anabolism plays a critical role in OA development. Our results suggest that circSLC7A2 may serve as a new therapeutic target for osteoarthritis.

Mechanism of Modified Danggui Sini Decoction for Knee Osteoarthritis Based on Network Pharmacology and Molecular Docking.

OBJECTIVE: This study aimed to explore the mechanism of Modified Danggui Sini Decoction in the treatment of knee osteoarthritis via a combination of network pharmacology and molecular docking. METHODS: The main chemical components and corresponding targets of Modified Danggui Sini Decoction were searched and screened in TCMSP database. The disease targets of knee osteoarthritis were summarized in GeneCards, OMIM, PharmGkb, TTD, and DrugBank databases. The visual interactive network of "drugs-active components-disease targets" was drawn by Cytoscape 3.8.1 software. The protein-protein interaction network was constructed by STRING database. Then, GO function and KEGG pathway enrichment were analyzed by Bioconductor/R, and the pathway of the highest degree of correlation with knee osteoarthritis was selected for specific analysis. Finally, molecular docking was used to screen and verify core genes by AutoDockTools software. RESULTS: Seventy-one main components of Modified Danggui Sini Decoction and 116 potential therapeutic targets of knee osteoarthritis were selected. The KEGG pathway and the GO function enrichment analysis showed that the targets of Modified Danggui Sini Decoction in the treatment of knee osteoarthritis were mainly concentrated on PI3K-Akt signaling pathway, TNF signaling pathway, IL-17 signaling pathway, apoptosis signaling pathway, Toll-like receptor signaling pathway, Th17 cell differentiation signaling pathway, HIF-1 signaling pathway, and NF-κB signaling pathway. It mainly involved inflammatory reaction, regulation of apoptotic signaling pathway, cellular response to regulation of inflammatory response, cellular response to oxidative stress, and other biological processes. The molecular docking results showed that ESR1-wogonin, MAPK1-quercetin, RELA-wogonin, RELA-baicalein, TP53-baicalein, TP53-quercetin, and RELA-quercetin have strong docking activities. CONCLUSION: Modified Danggui Sini Decoction has the hierarchical network characteristics of "multicomponent, multitarget, multifunction, and multipathway" in the treatment of knee osteoarthritis. It mainly regulates the proliferation and apoptosis of chondrocytes by regulating the PI3K-Akt signaling pathway and establishes cross-talk with many downstream inflammatory-related pathways to reduce the overall inflammatory response. Meanwhile, HIF-1 expression was used to ensure the normal function and metabolism of knee joint under hypoxia condition, and the above processes play a key role in the treatment of knee osteoarthritis.

Cyclin-Dependent Kinase 9 (CDK9) Inhibitor Atuveciclib Suppresses Intervertebral Disk Degeneration via the Inhibition of the NF-κB Signaling Pathway.

Intervertebral disk degeneration (IVDD) is a spinal disk condition caused by an inflammatory response induced by various proinflammatory cytokines, such as interleukin (IL)-1ß and tumor necrosis factor (TNF)-α. cyclin-dependent kinase 9 (CDK9) is a transcriptional regulator and potential therapeutic target for many diseases, especially in regulating the activation of primary inflammatory response genes. Our study investigated a highly selective CDK9 inhibitor, atuveciclib, which protects nucleus pulposus (NP) cells from proinflammatory stimuli-induced catabolism. The effects of CDK9 inhibition were determined in human and rat NP cells treated with IL-1ß in the presence or absence of atuveciclib or small interfering RNA target CDK9. Inhibition of CDK9 led to the attenuation of inflammatory response. In addition, rat intervertebral disk (IVD) explants were used to determine the role of CDK9 inhibition in extracellular matrix degradation. The rat IVDD model also proved that CDK9 inhibition attenuated IVDD, as validated using magnetic resonance imaging and immunohistochemistry. Taken together, CDK9 is a potential therapeutic target to prevent IVDD.

Topological Phase Transitions in Disordered Electric Quadrupole Insulators.

We investigate disorder-driven topological phase transitions in quantized electric quadrupole insulators in two dimensions. We show that chiral symmetry can protect the quantization of the quadrupole moment q_{xy}, such that the higher-order topological invariant is well defined even when disorder has broken all crystalline symmetries. Moreover, nonvanishing q_{xy} and consequent corner modes can be induced from a trivial insulating phase by disorder that preserves chiral symmetry. The critical points of such topological phase transitions are marked by the occurrence of extended boundary states even in the presence of strong disorder. We provide a systematic characterization of these disorder-driven topological phase transitions from both bulk and boundary descriptions.

An investigation and validation of CT scan in detection of spinal epidural adipose tissue.

To investigate the accuracy of computed tomography (CT) in evaluating spinal epidural adipose tissue compared to magnetic resonance imaging (MRI).CT scan images and matched magnetic resonance images of total 368 patients between July 2014 and July 2016 were evaluated. Hounsfield units (HU) of epidural fat (EF), dural sac (DuS), ligamentum flavum, bone of facet joints, and paraspinal muscles were measured for comparison. Anteroposterior diameter of the EF, anteroposterior diameter of the DuS, transverse diameter of the DuS, cross-sectional area of the EF, and cross-sectional area of the DuS were measured at each disc level from L1-2 to L5-S1.Fat tissue showed exclusive negative HU significantly different from all other periphery tissues. Pearson correlation coefficient analyses showed significant positive correlations between CT and MRI measurements; Bland-Altman plots also depicted satisfied agreement. Overgrowth of spinal EF was more commonly found at L2-3 and L3-4 levels in present study, and body weight, age, and gender were significantly associated with amounts of EF both on CT and MRI.The CT scan is a satisfied alternative of MRI for the evaluation of spinal epidural adipose tissue.

Flavopiridol Protects Bone Tissue by Attenuating RANKL Induced Osteoclast Formation.

Bone resorption and homeostasis is carried out by osteoclasts, whose differentiation and activity are regulated by the RANK/RANKL axis. Our previous studies using a mouse model of joint injury show that joint trauma induces local inflammation followed by bone remodeling. The transcription factor cyclin-dependent kinase 9 (CDK9) is the major regulator of inflammation, as CDK9 inhibitor flavopiridol effectively suppress injury-induced inflammatory response. The objective of this study was to investigate the underlying mechanism through which flavopiridol regulates bone resorption. The effects of CDK9 inhibition, by the specific-inhibitor flavopiridol, on bone resorption were determined in vivo using two distinct and clinically relevant bone remodeling models. The first model involved titanium particle-induced acute osteolysis, and the second model was ovariectomy-induced chronic osteoporosis. The effects and mechanism of CDK9 inhibition on osteoclastogenesis were examined using in vitro culture of bone marrow macrophages (BMMs). Our results indicated that flavopiridol potently suppressed bone resorption in both in vivo bone-remodeling models. In addition, CDK9 inhibition suppressed in vitro osteoclastogenesis of BMM and reduced their expression of osteoclast-specific genes. Finally, we determined that flavopiridol suppressed RANKL signaling pathway via inhibition of p65 phosphorylation and nuclear translocation of NF-κB. Summary, CDK9 is a potential therapeutic target to prevent osteolysis and osteoporosis by flavopiridol treatment.

Vertebral heights and ratios are not only race-specific, but also gender- and region-specific: establishment of reference values for mainland Chinese.

This study established gender-specific reference values in mainland Chinese (MC) and is important for quantitative morphometry for diagnosis and epidemiological study of osteoporotic vertebral compressive fracture. Comparisons of reference values among different racial populations are then performed to demonstrate the MC-specific characteristic. PURPOSE: Osteoporotic vertebral compressive fracture (OVCF) is a common complication of osteoporosis in the elder population. Clinical diagnosis and epidemiological study of OVCF often employ quantitative morphometry, which relies heavily on the comparison of patients' vertebral parameters to existing reference values derived from the normal population. Thus, reference values are crucial in clinical diagnosis. To our knowledge, this is the first study to establish reference values of the mainland Chinese (MC) for quantitative morphometry. METHODS: Vertebral heights including anterior (Ha), middle (Hm), posterior (Hp) heights, and predicted posterior height (pp) from T4 to L5 were obtained; and ratios of Ha/Hp, Hm/Hp and Hp/pp. were calculated from 585 MC (both female and male) for establishing reference values and subsequent comparisons with other studies. RESULTS: Vertebral heights increased progressively from T4 to L3 but then decreased in L4 and L5. Both genders showed similar ratios of vertebral dimensions, but male vertebrae were statistically larger than those of female (P < 0.01). Vertebral size of MC population was smaller than that of US and UK population, but was surprisingly larger than that of Hong Kong Chinese, although these two are commonly considered as one race. Data from different racial populations showed similar dimensional ratios in all vertebrae. CONCLUSIONS: We established gender-specific reference values for MC. Our results also indicated the necessity of establishing reference values that are not only race- and gender-specific, but also population- or region-specific for accurate quantitative morphometric assessment of OVCF.

Coexistence of harmonic soliton molecules and rectangular noise-like pulses in a figure-eight fiber laser.

We report the coexistence of high-order harmonic soliton molecules and rectangular noise-like pulses (NLP) in a figure-eight fiber laser mode-locked by a nonlinear amplifying loop mirror. The harmonic soliton molecule has a repetition rate of 936.6 MHz, corresponding to the 466th harmonics of the fundamental cavity repetition rate, with soliton separation of 16.5 ps. Meanwhile, the rectangular NLP operates at the fundamental repetition rate. In addition, these two types of pulses could be generated independently by manipulating the polarization controllers. The experimental results demonstrate an interesting operation regime of the fiber laser and contribute to enriching the dynamics of mode-locked pulses in fiber lasers.

Photonic crystal fiber for supporting 26 orbital angular momentum modes.

We propose and numerically investigate a photonic crystal fiber (PCF) based on As2S3 for supporting the orbital angular momentum (OAM) modes up to 26. The designed PCF is composed of four well-ordered air hole rings in the cladding and an air hole at the center. The OAM modes can be well separated due to the large effective index difference of above 10-4 between the eigenmodes and maintain single-mode condition radially. In addition, the dispersions of the modes increase slowly with wavelengths, while the confinement loss keeps as low as 10-9 dB/m. The proposed PCF increases the supported OAM modes which could have some potential applications in short-distance, high-capacity transmission.

Cyclin-dependent kinase 9 inhibition protects cartilage from the catabolic effects of proinflammatory cytokines.

OBJECTIVE: Cyclin-dependent kinase 9 (CDK-9) controls the activation of primary inflammatory response genes. The purpose of this study was to determine whether CDK-9 inhibition protects cartilage from the catabolic effects of proinflammatory cytokines. METHODS: Human chondrocytes were challenged with different proinflammatory stimuli (interleukin-1ß [IL-1ß], lipopolysaccharides, and tumor necrosis factor α) in the presence or absence of either the CDK-9 inhibitor flavopiridol or small interfering RNA (siRNA). The expression of messenger RNA (mRNA) for inflammatory mediator genes, catabolic genes, and anabolic genes were determined by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis. Cartilage explants were incubated for 6 days with IL-1ß in the presence or absence of flavopiridol. Cartilage matrix degradation was assessed by the release of glycosaminoglycan (GAG) and cleaved type II collagen (COL2A) peptides. RESULTS: CDK-9 inhibition by flavopiridol or knockdown by siRNA effectively suppressed the induction of mRNA for inducible nitric oxide synthase by all 3 proinflammatory stimuli. Results from NF-κB-targeted PCR array analysis showed that flavopiridol suppressed IL-1ß induction of a broad range of inflammatory mediator genes (59 of 67 tested). CDK-9 inhibition also suppressed the induction of catabolic genes (matrix metalloproteinase 1 [MMP-1], MMP-3, MMP-9, MMP-13, ADAMTS-4, and ADAMTS-5), but did not affect the basal expression of anabolic genes (COL2A, aggrecan, and cartilage oligomeric matrix protein) and housekeeping genes. Flavopiridol had no apparent short-term cytotoxicity, as assessed by G6PDH activity. Finally, in IL-1ß-treated cartilage explants, flavopiridol reduced the release of the matrix degradation product GAG and cleaved COL2A peptides, but did not affect long-term chondrocyte viability. CONCLUSION: CDK-9 activity is required for the primary inflammatory response in chondrocytes. Flavopiridol suppresses the induction of inflammatory mediator genes and catabolic genes to protect cartilage from the deleterious effects of proinflammatory cytokines, without affecting cell viability and functions.