DigitalUM :: Browsing by Subject "Chondrocyte"

Browsing by Subject "Chondrocyte"

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Open Access
Age-related degeneration of articular cartilage in the pathogenesis of osteoarthritis: molecular markers of senescent chondrocytes
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Musumeci, Giuseppe; Szychlinska, Marta Anna; Mobasheri, Ali
Aging is a natural process by which every single living organism approaches its twilight of existence in a natural way. However, aging is also linked to the pathogenesis of a number of complex diseases. This is the case for osteoarthritis (OA), where age is considered to be a major risk factor of this important and increasingly common joint disorder. Half of the world's population, aged 65 and older, suffers from OA. Although the relationship between the development of OA and aging has not yet been completely understood, it is thought that age-related changes correlate with other risk factors. The most prominent hypothesis linking aging and OA is that chondrocytes undergo premature aging due to several factors, such as excessive mechanical load or oxidative stress, which induce the so called “stress-induced senescent state”, which is ultimately responsible for the onset of OA. This review focuses on molecular markers and mechanisms implicated in chondrocyte aging and the pathogenesis of OA. We discuss the most important age-related morphological and biological changes that affect articular cartilage and chondrocytes. We also identify the main senescence markers that may be used to recognize molecular alterations in the extracellular matrix of cartilage as related to senescence. Since the aging process is strongly associated with the onset of osteoarthritis, we believe that strategies aimed at preventing chondrocyte senescence, as well as the identification of new increasingly sensitive senescent markers, could have a positive impact on the development of new therapies for this severe disease.
Open Access
Brefeldin A influences the cell surface abundance and intracellular pools of low and high ouabain affinity Na+, K+-ATPase cx subunit isoforms in articular chondrocytes
(Murcia : F. Hernández, 1999) Mobasheri, A.
The catalytic a isoforms of the Na+, K+- ATPase and stimuli controlling the plasma membrane abundance and intracellular distribution of the enzyme were studied in isolated bovine articular chondrocytes which have previously been shown to express low and high ouabain affinity a isoforms (a1 and a 3 respectively; al>>a3). The Naf, K+-ATPase density of isolated chondrocyte preparations was quantified by specific 3 ~ - ouabain binding. Long-term elevation of extracellular medium [Na+] resulted in a significant (31%; p<0.05) upregulation of Na+, K+-ATPase density and treatment with various pharmacological inhibitors (Rrefeldin A, monensin and cycloheximide) significantly @<0.001) blocked the upregulation. The subcellular distribution of the NaC, K+-ATPase a isoforms was examined by immunofluorescence confocal laser scanning microscopy which revealed predominantly plasma membrane immunostaining of a subunits in control chondrocytes. In Brefeldin A treated chondrocytes exposed to high [Na+], Na+, K+-ATPase a isoforms accumulated in juxta-nuclear pools and plasma membrane Na+, K+- ATPase density monitored by 3~-ouaba inb inding was significantly down-regulated due to Brefeldin A mediated disruption of vesicular transport. There was a marked increase in intracellular a 1 and a3 staining suggesting that these isoforms are preferentially upregulated following long-term exposure to high extracellular [Na+]. The results demonstrate that Na+, K+-ATPase density in chondrocytes is elevated in response to increased extracellular [Na+] through de novo protein synthesis of new pumps containing a 1 and a 3 isoforms, delivery via the endoplasrnic reticulum- Golgi complex constitutive secretory pathway and insertion into the plasma membrane.
Open Access
Co-localization of integrins and matrix metalloproteinases in the extracellular matrix of chondrocyte cultures
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2001) Schulze Tanzil, Gundula; de Souza, P.; Merker, H. J.; Shakibaei, M.
ß1-int eg rin s we re found in th e ca rtil age matri x, suggesting their implication in the assembly of its architectural sca ffold , but the mechanism fo r this event is not yet clear. Matrix metalloproteinases (MMPs) may be involved in an int egrin -shedding mechanism and matri x 131- integrins may ac t to alter MMP activity. To begin to address this qu esti o n, this stud y was desig ned to determin e wheth er ß1-in teg rin s and MMPs arc colocali zed in th e chondrocy tes or in the ex trace llul ar matrix of cartil age. We investigated high-densit y cultures of limb buds of 12-day -old mo use embryos by double immunoflu o re ce nce, immun oe lectron mi c rosco py and by coimmunoprccipitation assays in order to examine the loca li za ti o n o f ß1-int egrin s and matri x me ta ll oproteinases (MMP-1, MMP-3 and MMP-9) in cartilage. It was found , that all investigated MMPs and 13 1- integrins we re specifically co-loca li zed in high-density cartil age cultures. Immunogold and immunofluorescence labelling of both ß1-integrins and MMPs were observed not only at the surface of chondrocytes but mainl y also in th e pe rice llul ar space a nd distributed be tw ee n coll agen fibrils in th e ex trace llular matrix (ECM) as we ll. Res ults o f immun oprecipitati o n ex pe riments suggest a fun cti onal assoc iati on of MMPs and 13 Lintegrins in chondrocytes as already described fo r other cell types. Further investigations are needed to elu cidate the fun ctional association between Bl-integrins and MMPs in chondrocytes.
Open Access
Effects of the antirheumatic remedy Hox alpha - a new stinging nettle leaf extract - on matrix metalloproteinases in human chondrocytes in vitro
(Murcia : F. Hernández, 2002) Schulze-Tanzil, C.; Souza, P.H.de; Behnke, B.; Klingelhoefer, S.; Scheid, A.; Shakibaei, M.
Inflammatory joint diseases are characterized by enhanced extracellular matrix degradation which is predominantly mediated by cytokine-stimulated upregulation of matrix metalloproteinase (MMP) expression. Besides tumour necrosis factor-a ( T N F -a) , Interleukin-1ß (IL-1ß) produced by articular chondrocytes and synovial macrophages, is the most important cytokine stimulating MMP expression under inflammatory conditions. Blockade of these two cytokines and their downstream effectors are suitable molecular targets of antirheumatic therapy. Hox alpha is a novel stinging nettle (Urtica dioica/Urtica urens) leaf extract used for treatment of rheumatic diseases. The aim of the present study was to clarify the effects of Hox alpha and the monosubstance 13-HOTrE (13-Hydroxyoctadecatrienic acid) on the expression of matrix metalloproteinase-1, -3 and -9 proteins (MMP-1, -3, -9). Human chondrocytes were cultured on collagen type-II-coated petri dishes, exposed to IL-1ß and treated with or without Hox alpha and 13-HOTrE. A close analysis by immunofluorescence microscopy and western blot analysis showed that Hox alpha and 13- H O TrE significantly suppressed IL-1ß-induced expression of matrix metalloproteinase-1, -3 and –9 proteins on the chondrocytes in vitro. The potential of Hox alpha and 13-HOTrE to suppress the expression of matrix metalloproteinases may explain the clinical efficacy of stinging nettle leaf extracts in treatment of rheumatoid arthritis. These results suggest that the monosubstance 13-HOTrE is one of the more active antiinflammatory substances in Hox alpha and that Hox alpha may be a promising remedy for therapy of inflammatory joint diseases.
Open Access
Expression of long-chain noncoding RNA GAS5 in osteoarthritis and its effect on apoptosis and autophagy of osteoarthritis chondrocytes
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Ji, Qinghui; Qiao, Xiaofeng; Liu, Yongxiang; Wang, Dawei
Objective. To investigate the expression of long-chain noncoding RNA GAS5 in osteoarthritis(OA) and the effect of silencing GAS5 on autophagy of osteoarthritis chondrocytes (OACs). Methods. OA rat models were constructed by cutting the anterior cruciate ligament, and the expressions of GAS5 in rat cartilage tissues at 4 weeks (early OA) and 12 weeks (late OA) after modeling were detected. The rat chondrocytes were isolated, cultured and transfected with si-GAS5 to silencing GAS5. Then, the changes of apoptosis and autophagy levels of OA chondrocytes were detected by transfection of GFP-LC3 and flow cytometry. Bioinformatic tools were used to analyze the miRNA binding to GAS5 and the downstream target genes, then luciferase reporter assay and GDC-0349 (inhibitor of mTOR) were used to verify their relationships. Results. The expression of GAS5 in cartilage tissue of OA rats was higher than control, which was higher in late OA than that in early OA. After silencing the GAS5, the autophagy ability of OACs was increased and the apoptosis rate was decreased. GAS5 was able to bind to miR-144 and regulate the expressin of mTOR. mTOR inhibitor GDC-0349 could reverse the inhibition of GAS5 on autophagy but could not reverse its effect on apoptosis. Conclusion. GAS5 expresses highly in OA cartilage tissues and increases with the progression of OA. GAS5 inhibits autophagy and promotes the apoptosis of OACs, and the inhibition of autophagy may be related to its regulation of mTOR
Open Access
Glucose transport and metabolism in chondrocytes: a key to understanding chondrogenesis, skeletal development and cartilage degradation in osteoarthritis
(Murcia : F. Hernández, 2002) Mobasheri, A.; Vannucci, S.J.; Bondy, C.A.; Carter, S.D.; Innes, J.F.; Arteaga, M.F.; Trujillo, E.; Ferraz, I.; Shakibaei, M.; Martín Vasallo, P.
Despite the recognition that degenerative cartilage disorders like osteoarthritis (OA) and osteochondritis dissecans (OCD) may have nutritional abnormalities at the root of their pathogenesis, balanced dietary supplementation programs have played a secondary role in their management. This review emphasizes the importance and role of nutritional factors such as glucose and glucose-derived sugars (i.e. glucosamine sulfate and vitamin C) in the development, maintenance, repair, and remodeling of cartilage. Chondrocytes, the cells of cartilage, consume glucose as a primary substrate for ATP production in glycolysis and utilize glucosamine sulfate and other sulfated sugars as structural components for extracellular matrix synthesis and are dependant on hexose uptake and delivery to metabolic and biosynthetic pools. Data from several laboratories suggests that chondrocytes express multiple isoforms of the GLUT/SLC2A family of glucose/polyol transporters. These facilitative glucose transporter proteins are expressed in a tissue and cell-specific manner, exhibit distinct kinetic properties, and are developmentally regulated. They may also be regulated by endocrine factors like insulin and insulin-like growth factor I (IGF-I) and cytokines such as interleukin 1 beta (IL-1ß) and tumour necrosis factor alpha (TNF-a). Recent studies suggest that degeneration of cartilage may be triggered by metabolic disorders of glucose balance and that OA occurs coincident with metabolic disease, endocrine dysfunction and diabetes mellitus. Based on these metabolic, endocrine and developmental considerations we present a novel hypothesis regarding the role of glucose transport and metabolism in cartilage physiology and pathophysiology and speculate that supplementation with sugar-derived vitamins and nutraceuticals may benefit patients with degenerative joint disorders.
Open Access
Hypoxia inducible factor-1 and facilitative glucose transporters GLUT1 and GLUT3: Putative molecular components of the oxygen and glucose sensing apparatus in articular chondrocytes
(Murcia : F. Hernández, 2005) Mobasheri, A.; Richardson, S.; Mobasheri, R.; Shakibaei, M.; Hoyland, J.A.
Articular cartilage is an avascular connective tissue in which the availability of oxygen and glucose is significantly lower than synovial fluid and plasma. Glucose is an important metabolic fuel and structural precursor that plays a key role in the synthesis of extracellular matrix macromolecules in articular cartilage. However, glucose concentrations in cartilage can fluctuate depending on age, physical activity and endocrine status. Chondrocytes are glycolytic cells and must be able to sense the quantities of oxygen and glucose available to them in the extracellular matrix and respond appropriately by adjusting cellular metabolism. Consequently chondrocytes must have the capacity to survive in an extracellular matrix with limited nutrients and low oxygen tensions. The molecular mechanisms responsible for allowing chondrocytes to adapt to these harsh environmental conditions are poorly understood. In this article we present a novel “dual” model of oxygen and glucose sensing in chondrocytes based on recent experimental data. This model incorporates the hypoxiainducible factor alpha (HIF-1a) as an oxygen sensor and the hypoxia responsive facilitative glucose transporters, GLUT1 and GLUT3 as putative components of the glucose sensing apparatus in chondrocytes. Recent studies have shown that GLUT1 and GLUT3 are both expressed in chondrocytes and their HIF-1a-mediated transcription may be dually stimulated in response to hypoxia and low glucose conditions which in turn promote anaerobic glycolysis in favor of oxidative phosphorylation. This working model provides, for the first time, a unifying hypothesis to explain how chondrocytes might sense and respond to low oxygen tensions and alterations in extracellular glucose.
Open Access
Impact of the complement cascade on posttraumatic cartilage inflammation and degradation
(Murcia : F. Hernández, 2007) John, T.; Stahel, P.F.; Morgan, S.J.; Schulze-Tanzil, G.
The limited ability of articular cartilage to recover from injury, remains an unsolved clinical challenge in orthopaedic surgery. Persistent injury of the articular surface can lead to the development of posttraumatic osteoarthritis. The local inflammatory response contributes to the pathogenesis of osteoarthritis by inducing chondrocyte apoptosis and the de-regulation of chondrocyte matrix remodelling. The role of the complement system in contributing to secondary inflammation-mediated cartilage degradation represents a newer field of investigation. The purpose of this review article is to summarize the known complementmediated actions in cartilage homeostasis and injury. This article focuses on the known effects of complement on secondary chondrocyte apoptosis, and the interplay of the complement system with pro-inflammatory cytokines. Pharmacological therapies related to complement inhibition will be discussed as they potentially represent a new avenue for attenuating the effect of the complement system on cartilage repair.
Open Access
Induction of high temperature requirement A1, a serine protease, by TGF-beta1 in articular chondrocytes of mouse models of OA
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Xu, Lin; Golshirazian, Imanoel; Asbury, Brian J.; Li, Yefu
The goal of this study is to determine whether transforming growth factor beta 1 (Tgf-ß1) induces the high temperature requirement A1 (HtrA1) in articular chondrocytes of two mouse models of osteoarthritis (OA). Early onset articular cartilage degeneration in the mouse models was characterized by histology. Expression profiles of Tgf-ß1, p-Smad1, pSmad2/3 and HtrA1 in knee joints of the mouse models were examined by immunofluorescene. By in vitro and ex vivo experiments, human primary chondrocytes and articular cartilages from femoral condyles of mice were treated with recombinant human TGF-ß1 and an ALK5 chemical inhibitor, SB431542. The level of HTRA1 mRNA in human and mouse articular chondrocytes was examined by real-time PCR. Chondrocyte clusters were present in the articular cartilage of knee joints in the mouse models. Increased expressions of Tgf-ß1, pSmad2/3 and HtrA1 were detected in the articular chondrocyte of knee joints in the mouse models. The increased expressions of p-Smad2/3 and HtrA1 were colocalized in the articular chondrocyte of the knee joints. The expression of p-Smad1 was hardly detectable in the mouse models and their corresponding wild-type littermates. The level of HTRA1 mRNA was increased in human and mouse articular chondrocytes treated with TGF-ß1, compared with that in chondrocytes without the treatment of TGF-ß1. The TGF-ß1-induced expression of HTRA1 in human and mouse articular chondrocytes was inhibited by SB431542. These results suggest that the Tgf-ß1 canonical signaling was activated to induce HtrA1 in the articular chondrocytes of the mouse models of OA.
Open Access
Interleukin-18 induces apoptosis in human articular chondrocytes
(Murcia : F. Hernández, 2007) John, T.; Kohl, B.; Mobasheri, A.; Ertel, W.; Shakibaei, M.
Elevated levels of the pro-inflammatory cytokine, interleukin-18 (IL-18) have recently been demonstrated in osteoarthritic cartilage. However, the effects of IL-18 on chondrocyte signalling and matrix biosynthesis are poorly understood. Therefore, the present study was undertaken to further characterize the impact of IL-18 on human articular chondrocyte in vitro. Human articular chondrocytes were stimulated with various concentrations of recombinant human IL-18 (1, 10, 100 ng/ml) for 0, 4, 8, 12, 24, 48, 72 h in vitro. The effects of IL-18 on the cartilage-specific matrix protein collagen type II, the cytoskeletal protein vinculin, the cell matrix signal transduction receptor ß-integrin, key signalling proteins of the MAPKinase pathway (such as SHC (Sarc Homology Collagen) and activated MAPKinase [ERK-1/-2]), the pro-inflammatory enzyme cyclo-oxygenase-2 (COX-2) and the apoptosis marker activated caspase-3 were evaluated by Western blot analysis and immunofluorescence labelling. Morphological features of IL-18 stimulated chondrocytes were estimated by transmission electron microscopy. IL-18 lead to inhibition of collagen type IIdeposition, decreased ß-integrin receptor and vinculin synthesis, SHC and MAPKinase activation, increased COX-2 synthesis and activation of caspase-3 in chondrocytes in a time- and dose-dependent manner. Furthermore, chondrocytes treated with IL-18 exhibited typical morphological features of apoptosis as revealed by transmission electron microscopy. Taken together, the results of the present study underline key catabolic events mediated by IL-18 signalling in chondrocytes such as loss of cartilagespecific cartilagespecific matrix and apoptosis. Inhibition of MAPKinase signalling is hypothesized to contribute to these features. Future therapeutics targeting IL-18 signalling pathways may be beneficial in rheumatoid arthritis and osteoarthritis therapy.
Open Access
Interleukin-1ß-induced expression of the urokinase-type plasminogen activator receptor and its co-localization with MMPs in human articular chondrocytes
(Murcia : F. Hernández, 2004) Schwab, W.; Schulze-Tanzil, G.; Mobasheri, A.; Dressler, J.; Kotzsch, M.; Shakibaei, M.
The urokinase-type plasminogen activator receptor (uPAR) plays a critical role in cartilage degradation during osteoarthritis as it regulates pericellular proteolysis mediated by serine proteinases. Another important family of proteinases responsible for ECM destruction in arthritis are the matrix metalloproteinases (MMPs). MMPs are regulated by IL- 1ß, a cytokine that plays a pivotal role in pathogenesis of osteoarthritis. This study was undertaken to address two questions: 1. Is uPAR-expression regulated by proinflammatory cytokines such as IL-1ß? 2. Does a functional co-localization exist between uPAR and MMPs? By immunohistochemical analysis we observed enhanced expression of uPAR on chondrocytes derived from osteoarthritic human cartilage compared to nonosteoarthritic controls. We found an IL-1ß-mediated expression of uPAR by immunoelectron microscopy. Western blot analysis demonstrated that IL-1ßstimulated expression of uPAR on chondrocytes in vitro increased in a dose-dependent manner. Furthermore, we found a functional co-localization between uPAR and MMP-9 on IL-1ß-stimulated chondrocytes by means of a co-immunoprecipitation assay. Expression of uPAR in osteoarthritic cartilage but not in healthy cartilage suggests that uPAR plays a role in cartilage breakdown. We propose that uPAR-mediated effects e.g. pericellular proteolysis are one of other cytokine (IL-1ß)-mediated events that contribute to the pathogenesis of osteoarthritis. Furthermore, we found that MMPs and uPAR were part of the same cell surface complexes in chondrocytes. This finding underlines a functional interaction between MMPs and the serine proteinase system in the fine regulation of pericellular proteolysis. Interfering with uPAR signaling may present a novel target in arthritis therapy to prevent excessive proteolytic degradation.
Open Access
Ion transport in chondrocytes, membrane transporters involved in intracellular ion homeostasis and the regulation of cell volume, free [Ca2+] and pH
(Murcia : F. Hernández, 1998) Mobasheri, A.; Mobasheri, R.; Francis, M.J.O.; Trujillo, E.; Alvarez de la Rosa, D.; Martín Vasallo, P.
Chondrocytes exist in an unusual and variable ionic and osmotic environment in the extracellular matrix of cartilage and are responsible for maintaining the delicate equilibrium between extracellular matrix synthesis and degradation. The mechanical performance of cartilage relies on the biochemical properties of the matrix. Alterations to the ionic and osmotic extracellular environment of chondrocytes have been shown to influence the volume, intracellular pH and ionic content of the cells, which in turn modify the synthesis and degradation of extracellular matrix macromolecules. Physiological ion homeostasis is fundamental to the routine functioning of cartilage and the factors that control the integrity of this highly evolved and specialized tissue. Ion transport in cartilage is relatively unexplored and the biochemical properties and molecular identity of membrane transport mechanisms employed by chondrocytes in the control of intracellular ion concentrations and pH is not fully defined and this review focuses on these processes. Chondrocytes have been shown to express voltage and stretch activated ion channels, passive exchangers and ATP dependent ion pumps. In addition, recent studies of transport systems in chondrocytes have demonstrated the presence of isozyme diversity that includes Na+/H+ exchange (NHE1, NHE3), Na+, K+-ATPase (several isoforms) and others each of which possess considerably different kinetic properties and modes of regulation. This multitude of isozyme diversity indicates the highly specialized handling of ions and protons in order to accomplish a fine regulation of their transmembrane fluxes. The complexities of these transport systems and their patterns of isoform expression underscore the subtlety of ion homeostasis and pH regulation in normal cartilage. Perturbations in these mechanisms may affect the physiological turnover of cartilage and thus increase the susceptibility to degenerative joint disease.
Open Access
Recent studies on the biological action of parathyroid hormone {PTH)-related peptide (PTHrP) and PTH/PTHrP receptor in cartilage and bone
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2000) Amizuka, N.; Henderson, J. E.; White, J. H.; Karaplis, A. C.; Goltzman, D.; Sasaki, T.; Ozawa, H.
Mice with a targeted deletion of parathyroid hormone (PTH)-related peptide (PTHrP) develop a form of dyschondroplasia resulting from diminished proliferation and premature maturation of chondrocytes. Abnormal, heterogeneous populations of chondrocytes at different stages of differentiation were seen in the hypertrophic zone of the mutant growth plate. Although the homozygous null animals die within several hours of birth, mice heterozygous for PTHrP gene deletion reach adulthood, at which time they show evidence of osteopenia. Therefore, PTHrP appears to modulate cell proliferation and differentiation in both the pre and post natal period. PTH/PTHrP receptor expression in the mouse is controlled by two promoters. We recently found that, while the downstream promoter controls PTH/PTHrP receptor gene expression in bone and cartilage, it is differentially regulated in the two tissues. la,25-dihydroxyvitamin D3 downregulated the activity of the downstream promoter in osteoblasts, but not in chondrocytes, both in vivo and .in vitro. Most of the biological activity of PTHrP is thought to be mediated by binding of its amino terminus to the PTH/PTHrP receptor. However, recent evidence suggests that amino acids 87-107, outside of the amino terminal binding domain, act as a nucleolar targeting signal. Chondrocytic cell line, CFK2, transfected with wild-type PTHrP eDNA showed PTHrP in the nucleoli as well as in the secretory pathway. Therefore, PTHrP appears to act as a bifunctional modulator of both chondrocyte proliferation and differentiation, through signal transduction linked to the PTHIPTHrP receptor and by its direct action in the nucleolus.
Open Access
The hypertrophic chondrocyte: To be or not to be
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Hallett, Shawn A.; Ono, Wanida; Ono, Noriaki
Hypertrophic chondrocytes are the master regulators of endochondral ossification; however, their ultimate cell fates cells remain largely elusive due to their transient nature. Historically, hypertrophic chondrocytes have been considered as the terminal state of growth plate chondrocytes, which are destined to meet their inevitable demise at the primary spongiosa. Chondrocyte hypertrophy is accompanied by increased organelle synthesis and rapid intracellular water uptake, which serve as the major drivers of longitudinal bone growth. This process is delicately regulated by major signaling pathways and their target genes, including growth hormone (GH), insulin growth factor-1 (IGF-1), indian hedgehog (Ihh), parathyroid hormone-related protein (PTHrP), bone morphogenetic proteins (BMPs), sex determining region Y-box 9 (Sox9), runt-related transcription factors (Runx) and fibroblast growth factor receptors (FGFRs). Hypertrophic chondrocytes orchestrate endochondral ossification by regulating osteogenic-angiogenic and osteogenic-osteoclastic coupling through the production of vascular endothelial growth factor (VEGF), receptor activator of nuclear factor kappa-B ligand (RANKL) and matrix metallopeptidases-9/13 (MMP-9/13). Hypertrophic chondrocytes also indirectly regulate resorption of the cartilaginous extracellular matrix, by controlling formation of a special subtype of osteoclasts termed "chondroclasts". Notably, hypertrophic chondrocytes may possess innate potential for plasticity, reentering the cell cycle and differentiating into osteoblasts and other types of mesenchymal cells in the marrow space. We may be able to harness this unique plasticity for therapeutic purposes, for a variety of skeletal abnormalities and injuries. In this review, we discuss the morphological and molecular properties of hypertrophic chondrocytes, which carry out important functions during skeletal growth and regeneration.
Open Access
β-Ecdysone attenuates cartilage damage in a mouse model of collagenase-induced osteoarthritis via mediating FOXO1/ADAMTS-4/5 signaling axis
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Han, Junzhu; Guan, Jianzhong; Zhu, Xunbing
Background. β-Ecdysone has been reported to perform a protective effect to prevent interleukin 1β (IL-1β)-induced apoptosis and inflammatory response in chondrocytes. In our study, the chondroprotective effects of β-Ecdysone were explored in a mouse model of collagenase-induced osteoarthritis (OA). Methods. Injection of collagenase in the left knee was implemented to establish a mouse model of OA. The histomorphological analysis was detected using safranine O staining. Serum pro-inflammatory cytokines were measured by ELISA assays. Protein expression in the femur and chondrocytes was analyzed using western blot. Chondrocyte apoptosis was evaluated by terminaldeoxynucleoitidyl transferase mediated nick end labeling (TUNEL) staining. Results. Treatment of OA mice with β-Ecdysone supplementation significantly inhibited the production of pro-inflammatory cytokines. Histologic examination exhibited that the degradation of proteoglycans and the loss of trabecular bone were observed in collagenaseinjected mice. However, OA-like changes were attenuated by β-Ecdysone administration in collagenaseinjected mice. Both in vivo and in vitro models, nuclear forkhead box O1 (FOXO1) protein expression was significantly reduced in the femur of collagenase-treated mice and IL-1β-stimulated chondrocytes. However, βEcdysone treatment was able to rescue FOXO1 protein expression in the nucleus to inhibit the transcription and translation of a disintegrin-like and metallopeptidase (reprolysin type) with thrombospondin type 1 motif, 4 (ADAMTS-4) and ADAMTS-5. Conclusion. The findings suggested that β-Ecdysone functioned as a FOXO1 activator to protect collagenaseinduced cartilage damage. FOXO1 might be a potential molecular target of β-Ecdysone for the effective prevention and treatment of OA.

Browsing by Subject "Chondrocyte"

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