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Fulltext Colonies in engineered articular cartilage express superior differentiation

Selvaratnam L, Abd Rahim S, Kamarul T, Chan KY, Sureshan S, Penafort R, et al.

Med J Malaysia, 2005 Jul;60 Suppl C:49-52.
PMID: 16381284

In view of poor regeneration potential of the articular cartilage, in-vitro engineering of cartilage tissue offers a promising option for progressive joint disease. This study aims to develop a biologically engineered articular cartilage for autologous transplantation. The initial work involved determination of chondrocyte yield and viability, and morphological analysis. Cartilage was harvested from the knee, hip and shoulder joints of adult New Zealand white rabbits and chondrocytes were isolated by enzymatic digestion of the extra-cellular matrix before serial cultivation in DMEM/Ham's F12 media as monolayer cultures. No differences were noted in cell yield. Although chondrocytes viability was optimal (>93%) following harvest from native cartilage, their viability tended to be lowered on passaging. Chondrocytes aggregated in isogenous colonies comprising ovoid cells with intimate intracellular contacts and readily exhibited Safranin-O positive matrix; features typically associated with articular cartilage in-vivo. However, chondrocytes also existed concurrently in scattered bipolar/multipolar forms lacking Safranin-O expression. Therefore, early data demonstrated successful serial culture of adult chondrocytes with differentiated morphology seen in established chondrocyte colonies synthesizing matrix proteoglycans.

Matched MeSH terms: Chondrocytes/cytology*; Chondrocytes/physiology
Fulltext The properties of chondrocyte membrane reservoirs and their role in impact-induced cell death

Moo EK, Amrein M, Epstein M, Duvall M, Abu Osman NA, Pingguan-Murphy B, et al.

Biophys. J., 2013 Oct 1;105(7):1590-600.
PMID: 24094400 DOI: 10.1016/j.bpj.2013.08.035

Impact loading of articular cartilage causes extensive chondrocyte death. Cell membranes have a limited elastic range of 3-4% strain but are protected from direct stretch during physiological loading by their membrane reservoir, an intricate pattern of membrane folds. Using a finite-element model, we suggested previously that access to the membrane reservoir is strain-rate-dependent and that during impact loading, the accessible membrane reservoir is drastically decreased, so that strains applied to chondrocytes are directly transferred to cell membranes, which fail when strains exceed 3-4%. However, experimental support for this proposal is lacking. The purpose of this study was to measure the accessible membrane reservoir size for different membrane strain rates using membrane tethering techniques with atomic force microscopy. We conducted atomic force spectroscopy on isolated chondrocytes (n = 87). A micron-sized cantilever was used to extract membrane tethers from cell surfaces at constant pulling rates. Membrane tethers could be identified as force plateaus in the resulting force-displacement curves. Six pulling rates were tested (1, 5, 10, 20, 40, and 80 μm/s). The size of the membrane reservoir, represented by the membrane tether surface areas, decreased exponentially with increasing pulling rates. The current results support our theoretical findings that chondrocytes exposed to impact loading die because of membrane ruptures caused by high tensile membrane strain rates.

Matched MeSH terms: Chondrocytes/physiology; Chondrocytes/ultrastructure; Chondrocytes/chemistry*
Tissue engineering trachea: Malaysian experience

Aminuddin BS

Med J Malaysia, 2004 May;59 Suppl B:3-4.
PMID: 15468790

Management of severe tracheal anomalies remains a clinical challenge. Tissue engineering offers new hope in trachea reconstruction surgery. However to date no optimal technique achieved in the formation of human or animal trachea. The main problem lies on the biomaterial used and the complex city of forming trachea in vivo. This study was aimed at creating tissue-engineered trachea cartilage from easily accessible human and animal nasal septum cartilage using internal scaffold and biodegradable human and animal fibrin.

Matched MeSH terms: Chondrocytes/pathology; Chondrocytes/transplantation*
Human amniotic membrane as a chondrocyte carrier vehicle/substrate: in vitro study

Krishnamurithy G, Shilpa PN, Ahmad RE, Sulaiman S, Ng CL, Kamarul T

J Biomed Mater Res A, 2011 Dec 01;99(3):500-6.
PMID: 21913317 DOI: 10.1002/jbm.a.33184

Human amniotic membrane (HAM) is an established biomaterial used in many clinical applications. However, its use for tissue engineering purposes has not been fully realized. A study was therefore conducted to evaluate the feasibility of using HAM as a chondrocyte substrate/carrier. HAMs were obtained from fresh human placenta and were process to produced air dried HAM (AdHAM) and freeze dried HAM (FdHAM). Rabbit chondrocytes were isolated and expanded in vitro and seeded onto these preparations. Cell proliferation, GAG expression and GAG/cell expression were measured at days 3, 6, 9, 12, 15, 21, and 28. These were compared to chondrocytes seeded onto plastic surfaces. Histological analysis and scanning electron microscopy was performed to observe cell attachment. There was significantly higher cell proliferation rates observed between AdHAM (13-51%, P=0.001) or FdHAM (18-48%, p = 0.001) to chondrocytes in monolayer. Similarly, GAG and GAG/cell expressed in AdHAM (33-82%, p = 0.001; 22-60%, p = 0.001) or FdHAM (41-81%, p = 0.001: 28-60%, p = 0.001) were significantly higher than monolayer cultures. However, no significant differences were observed in the proliferation rates (p = 0.576), GAG expression (p = 0.476) and GAG/cell expression (p = 0.135) between AdHAM and FdHAM. The histology and scanning electron microscopy assessments demonstrates good chondrocyte attachments on both HAMs. In conclusion, both AdHAM and FdHAM provide superior chondrocyte proliferation, GAG expression, and attachment than monolayer cultures making it a potential substrate/carrier for cell based cartilage therapy and transplantation.

Matched MeSH terms: Chondrocytes/cytology; Chondrocytes/metabolism*; Chondrocytes/ultrastructure
Fulltext Development of a cartilage composite utilizing porous tantalum, fibrin, and rabbit chondrocytes for treatment of cartilage defect

Jamil K, Chua KH, Joudi S, Ng SL, Yahaya NH

J Orthop Surg Res, 2015;10:27.
PMID: 25889942 DOI: 10.1186/s13018-015-0166-z

Functional tissue engineering has emerged as a potential means for treatment of cartilage defect. Development of a stable cartilage composite is considered to be a good option. The aim of the study was to observe whether the incorporation of cultured chondrocytes on porous tantalum utilizing fibrin as a cell carrier would promote cartilage tissue formation.

Matched MeSH terms: Chondrocytes/cytology; Chondrocytes/metabolism; Chondrocytes/transplantation*
Fulltext The crosstalk between mesenchymal stem cells and damaged cartilage in osteoarthritis

Satar Jabbar Rahi Algraittee, Rajesh Ramasamy

Malaysian Journal of Medicine and Health Sciences, 2020;16(2):262-268.
MyJurnal

Human cartilage contains multipotent stem cells, namely mesenchymal stem cells (MSCs) which are progenitors of connective tissue that play homeostatic and reparative roles. Although the major constituent cells in the cartilage are chondrocytes, they possess a limited regenerative ability, and as a result, spontaneous cartilage repair by chondro- cytes leads to the synthesis of fibrocartilage. Similarly, MSCs derived from articular cartilage of osteoarthritis patients have demonstrated inadequacy in cartilage repair. The role of MSCs in the pathophysiology of osteoarthritis (OA) is not entirely understood, whether the inflammatory milieu associated with OA joints affects the reparative properties of MSCs or the inherent defects of OA cartilage-derived MSCs impair the proper execution of the required immu- nosuppressive and reparative functions. Therefore, the current review explores the biological characteristics and features of MSCs derived from physiological state and OA condition with the aim of identifying how OA affects MSC functions as well as the role of MSCs in the pathophysiology of OA.

Matched MeSH terms: Chondrocytes
Fulltext Curcumin minimises histopathological and immunological progression in the ankle joints of collagen-induced arthritis rats

Kevin, T.T.M., Nur Idanis, A.S., Anastasha, B., Mohd Faris, M.R., Faizah, O., Taty Anna, K.

Medicine & Health, 2020;15(2):26-36.
MyJurnal

Curcumin adalah satu rempah tradisional yang mempunyai potensi untuk menyembuhkan pelbagai jenis penyakit inflamatori, termasuk artritis. Kajian ini dijalankan untuk memerhatikan kesan-kesan curcumin ke atas perubahan histopatologi dan aras interleukin-1β (IL-1β) di dalam artritis aruhan kolagen (CIA). Tiga puluh ekor tikus jantan Sprague-Dawley (150+50 g) dibahagikan kepada lima kumpulan secara rawak. Satu kumpulan dijadikan kumpulan kawalan normal (CTRL), manakala selebihnya disuntik dengan 150 μg emulsi kolagen secara subkutan pada hari 0. Kumpulan CTRL dan CIA-Curcumin-d0 masing-masing diberi suplimentasi harian minyak zaitun oil (1 ml/kg) dan curcumin (110 mg/ml/ kg) bermula pada hari 0. Kumpulan CIA-OV (kawalan negatif), CIA-Beta dan CIA-Curcumin-d14 pula, masing-masing diberi suplimentasi harian minyak zaitun (1 ml/kg), Betamethasone (0.5 mg/ml/kg), dan curcumin (110 mg/ml/kg) bermula pada hari 14. Suplimentasi harian tersebut diberi kepada tikus-tikus sehingga hari ke 42. Kajian ini menunjukkan bahawa kumpulan CIA-Beta (**P=0.00) dan CIA-Curcumin-d0 (**P=0.01) masing-masing mempamerkan purata skor histologi yang lebih rendah secara signifikan berbanding kumpulan CIA-OV. Aras IL-1β di dalam serum untuk kumpulan CIA-Beta dan CIA-Curcumin-d0 tidak meningkat secara signifikan pada hari ke 42 berbanding hari 0. Purata peningkatan aras IL-1β dari hari 0 ke hari 42 juga adalah rendah secara signifikan (**P≤0.01) untuk semua kumpulan CIA berbanding kumpulan CIA-OV. Tidak terdapat perbezaan yang signifikan dalan purata skor histologi dan aras IL-1β kumpulan of CIA-Curcumin-d0 berbanding kumpulan CIA-Beta. Kesimpulannya suplimentasi awal curcumin berpotensi untuk meminimakan perubahan yang disebabkan penyakit artritis aruhan kolagen pada tikus.

Matched MeSH terms: Chondrocytes
Fulltext Autologous chondrocyte implantation for knee focal cartilage defects: 3 years' follow-up at the University Malaya Medical Centre

Abbas AA, Mohamad JA, Lydia AL, Selvaratnam L, Razif A, Ab-Rahim S, et al.

JUMMEC, 2014;17(1):8-13.
MyJurnal

Autologous chondrocyte implantation (ACI) is a widely accepted procedure for the treatment of large, fullthickness chondral defects involving various joints, but its use in developing countries is limited because of high cost and failure rates due to limited resources and support systems. Five patients (age

Matched MeSH terms: Chondrocytes
Effects of different media on the in vivo chondrogenesis of sheep bone marrow stem cells: histological assessment

Alfaqeh H, Chua KH, Aminuddin BS, Ruszymah BH

Med J Malaysia, 2008 Jul;63 Suppl A:119-20.
PMID: 19025014

This study aimed to compare the effects of three different media on the in vivo chondrogenesis of sheep bone marrow stem cells (BMSC). Sheep BMSC were cultured in F12:DMEM + 10% FBS, chondrogenic medium containing 5ng/ml TGF,3 + 50ng/ml IGF-1 and UKM-MECC for three weeks. The cultured cells were then harvested for construct formation with fibrin. Constructed tissues were implanted subcutaneously into nude mice for in vivo development. Cell aggregates were formed in both chondrogenic medium and UKM-MECC demonstrated the early chondrogenesis process. After five weeks of in vivo development, both chondrogenic medium and UKM-MECC promoted cartilage matrix synthesis confirmed by Safranin O staining.

Matched MeSH terms: Chondrocytes*
Fulltext Extracellular Vesicles in the Synovial Joint: Is there a Role in the Pathophysiology of Osteoarthritis?

Esa A, Connolly KD, Williams R, Archer CW

Malays Orthop J, 2019 Mar;13(1):1-7.
PMID: 31001376 DOI: 10.5704/MOJ.1903.012

The role of extracellular vesicles (EV) in osteoarthritis has become the focus of much research. These vesicles were isolated from several cell types found in synovial joint including chondrocytes and synovium. As articular cartilage is an avascular tissue surrounded by synovial fluid, it is believed that EV might play a crucial role in the homeostasis of cartilage and also could hold key information in the pathogenesis of osteoarthritis. This is thought to be due to activation of pro-inflammatory factors leading to a catabolic state and degradation of cartilage. In addition, due to the nature of articular cartilage lacking neuronal innervation, knowledge of EV can contribute to identification of novel biomarkers in this debilitating condition. This can be either directly isolated from aspirate of synovial fluid or from peripheral blood. Finally, EVs are known to shuttle important signalling molecules which can be utilised as unique modality in transferring therapeutic compounds in a cell free manner.

Matched MeSH terms: Chondrocytes
The effect of TGF-beta1 and beta-estradiol on glycosaminoglycan and type II collagen distribution in articular chondrocyte cultures

Ab-Rahim S, Selvaratnam L, Kamarul T

Cell Biol Int, 2008 Jul;32(7):841-7.
PMID: 18479947 DOI: 10.1016/j.cellbi.2008.03.016

Articular cartilage extracellular matrix (ECM) plays a crucial role in regulating chondrocyte functions via cell-matrix interaction, cytoskeletal organization and integrin-mediated signaling. Factors such as interleukins, basic fibroblast growth factor (bFGF), bone morphogenic proteins (BMPs) and insulin-like growth factor (IGF) have been shown to modulate the synthesis of extracellular matrix in vitro. However, the effects of TGF-beta1 and beta-estradiol in ECM regulation require further investigation, although there have been suggestions that these factors do play a positive role. To establish the role of these factors on chondrocytes derived from articular joints, a study was conducted to investigate the effects of TGF-beta1 and beta-estradiol on glycosaminoglycan secretion and type II collagen distribution (two major component of cartilage ECM in vivo). Thus, chondrocyte cultures initiated from rabbit articular cartilage were treated with 10ng/ml of TGF-beta1, 10nM of beta-estradiol or with a combination of both factors. Sulphated glycosaminoglycan (GAG) and type II collagen levels were then measured in both these culture systems. The results revealed that the synthesis of GAG and type II collagen was shown to be enhanced in the TGF-beta1 treated cultures. This increase was also noted when TGF-beta1 and beta-estradiol were both used as culture supplements. However, beta-estradiol alone did not appear to affect GAG or type II collagen deposition. There was also no difference between the amount of collagen type II and GAG being expressed when chondrocyte cultures were treated with TGF-beta1 when compared with cultures treated with combined factors. From this, we conclude that although TGF-beta1 appears to stimulate chondrocyte ECM synthesis, beta-estradiol fails to produce similar effects. The findings of this study confirm that contrary to previous claims, beta-estradiol has little or no effect on chondrocyte ECM synthesis. Furthermore, the use of TGF-beta1 may be useful in future studies looking into biological mechanisms by which ECM synthesis in chondrocyte cultures can be augmented, particularly for clinical application.

Matched MeSH terms: Chondrocytes/cytology; Chondrocytes/drug effects; Chondrocytes/metabolism*
Fulltext Oxygen tension modulates the effects of TNFα in compressed chondrocytes

Tilwani RK, Vessillier S, Pingguan-Murphy B, Lee DA, Bader DL, Chowdhury TT

Inflamm Res, 2017 Jan;66(1):49-58.
PMID: 27658702 DOI: 10.1007/s00011-016-0991-5

OBJECTIVE AND DESIGN: Oxygen tension and biomechanical signals are factors that regulate inflammatory mechanisms in chondrocytes. We examined whether low oxygen tension influenced the cells response to TNFα and dynamic compression.
MATERIALS AND METHODS: Chondrocyte/agarose constructs were treated with varying concentrations of TNFα (0.1-100 ng/ml) and cultured at 5 and 21 % oxygen tension for 48 h. In separate experiments, constructs were subjected to dynamic compression (15 %) and treated with TNFα (10 ng/ml) and/or L-NIO (1 mM) at 5 and 21 % oxygen tension using an ex vivo bioreactor for 48 h. Markers for catabolic activity (NO, PGE2) and tissue remodelling (GAG, MMPs) were quantified by biochemical assay. ADAMTS-5 and MMP-13 expression were examined by real-time qPCR. 2-way ANOVA and a post hoc Bonferroni-corrected t test were used to analyse data.
RESULTS: TNFα dose-dependently increased NO, PGE2 and MMP activity (all p

Matched MeSH terms: Chondrocytes/drug effects*; Chondrocytes/metabolism; Chondrocytes/physiology
Fulltext Effect of transforming growth factor-β2 on biological regulation of multilayer primary chondrocyte culture

Khaghani SAB, Akbarova G, Soon CF, Dilbazi G

Cell Tissue Bank, 2018 Dec;19(4):763-775.
PMID: 30377863 DOI: 10.1007/s10561-018-9732-z

Cytokines are extremely potent biomolecules that regulate cellular functions and play multiple roles in initiation and inhibition of disease. These highly specialised macromolecules are actively involved in control of cellular proliferation, apoptosis, cell migration and adhesion. This work, investigates the effect of transforming growth factor-beta2 (TGF-β2) on the biological regulation of chondrocyte and the repair of a created model wound on a multilayer culture system. Also the effect of this cytokine on cell length, proliferation, and cell adhesion has been investigated. Chondrocytes isolated from knee joint of rats and cultured at 4 layers. Each layer consisted of 2 × 105 cells/ml with and without TGF-β2. The expression of mRNA and protein levels of TGF-β receptors and Smad1, 3, 4, and 7 have been analysed by RT-PCR and western blot analysis. The effect of different supplementations in chondrocyte cell proliferation, cell length, adhesion, and wound repair was statistically analysed by One-way ANOVA test. Our results showed that the TGFβ2 regulates mRNA levels of its own receptors, and of Smad3 and Smad7. Also the TGF-β2 caused an increase in chondrocyte cell length, but decreased its proliferation rate and the wound healing process. TGF-β2 also decreased cell adhesion ability to the surface of the culture flask. Since, TGF-β2 increased the cell size, but showed negative effect on cell proliferation and adhesion of CHC, the effect of manipulated TGF-β2 with other growth factors and/or proteins needs to be investigated to finalize the utilization of this growth factor and design of scaffolding in treatment of different types of arthritis.

Matched MeSH terms: Chondrocytes/cytology*; Chondrocytes/drug effects; Chondrocytes/metabolism
Dual photon excitation microscopy and image threshold segmentation in live cell imaging during compression testing

Moo EK, Abusara Z, Abu Osman NA, Pingguan-Murphy B, Herzog W

J Biomech, 2013 Aug 9;46(12):2024-31.
PMID: 23849134 DOI: 10.1016/j.jbiomech.2013.06.007

Morphological studies of live connective tissue cells are imperative to helping understand cellular responses to mechanical stimuli. However, photobleaching is a constant problem to accurate and reliable live cell fluorescent imaging, and various image thresholding methods have been adopted to account for photobleaching effects. Previous studies showed that dual photon excitation (DPE) techniques are superior over conventional one photon excitation (OPE) confocal techniques in minimizing photobleaching. In this study, we investigated the effects of photobleaching resulting from OPE and DPE on morphology of in situ articular cartilage chondrocytes across repeat laser exposures. Additionally, we compared the effectiveness of three commonly-used image thresholding methods in accounting for photobleaching effects, with and without tissue loading through compression. In general, photobleaching leads to an apparent volume reduction for subsequent image scans. Performing seven consecutive scans of chondrocytes in unloaded cartilage, we found that the apparent cell volume loss caused by DPE microscopy is much smaller than that observed using OPE microscopy. Applying scan-specific image thresholds did not prevent the photobleaching-induced volume loss, and volume reductions were non-uniform over the seven repeat scans. During cartilage loading through compression, cell fluorescence increased and, depending on the thresholding method used, led to different volume changes. Therefore, different conclusions on cell volume changes may be drawn during tissue compression, depending on the image thresholding methods used. In conclusion, our findings confirm that photobleaching directly affects cell morphology measurements, and that DPE causes less photobleaching artifacts than OPE for uncompressed cells. When cells are compressed during tissue loading, a complicated interplay between photobleaching effects and compression-induced fluorescence increase may lead to interpretations in cell responses to mechanical stimuli that depend on the microscopic approach and the thresholding methods used and may result in contradictory interpretations.

Matched MeSH terms: Chondrocytes/cytology; Chondrocytes/metabolism*
Upregulation of matrix synthesis in chondrocyte-seeded agarose following sustained bi-axial cyclic loading

Pingguan-Murphy B, Nawi I

Clinics (Sao Paulo), 2012 Aug;67(8):939-44.
PMID: 22948463

OBJECTIVES: The promotion of extracellular matrix synthesis by chondrocytes is a requisite part of an effective cartilage tissue engineering strategy. The aim of this in vitro study was to determine the effect of bi-axial cyclic mechanical loading on cell proliferation and the synthesis of glycosaminoglycans by chondrocytes in three-dimensional cultures.
METHOD: A strain comprising 10% direct compression and 1% compressive shear was applied to bovine chondrocytes seeded in an agarose gel during two 12-hour conditioning periods separated by a 12-hour resting period.
RESULTS: The bi-axial-loaded chondrocytes demonstrated a significant increase in glycosaminoglycan synthesis compared with samples exposed to uni-axial or no loading over the same period (p<0.05). The use of a free-swelling recovery period prior to the loading regime resulted in additional glycosaminoglycan production and a significant increase in DNA content (p<0.05), indicating cell proliferation.
CONCLUSIONS: These results demonstrate that the use of a bi-axial loading regime results in increased matrix production compared with uni-axial loading.

Matched MeSH terms: Chondrocytes/cytology; Chondrocytes/metabolism*
Fulltext In-vitro differentiation study on isolated human mesenchymal stem cells

Mok PL, Cheong SK, Leong CF

Malays J Pathol, 2008 Jun;30(1):11-9.
PMID: 19108406 MyJurnal

Mesenchymal stem cells are pluripotent progenitors that could be found in human bone marrow. Mesenchymal stem cells are capable of renewing themselves without differentiation in long-term culture. These cells also have low immunogenicity and can suppress alloreactive T cell responses. In the current study, mesenchymal stem cells isolated and propagated previously from the bone marrow of a megaloblastic anaemia patient were tested for their capabilities to differentiate into adipocytes, chondrocytes and osteoblasts in vitro. The differentiated cells were determined by Oil Red O, Alcian Blue-PAS and Alizarin Red S staining, and reverse transcriptase-polymerase chain reaction to determine the expression of mRNA specific for adipogenesis, chondrogenesis and osteogenesis. The results showed that the fibroblast-like cells were capable of differentiating into adipocytes, chondrocytes and osteoblasts upon chemical induction. The adipocytes, chondrocytes and osteoblasts were stained positively to Oil Red O, Alcian Blue-PAS and Alizarin Red S respectively. The differentiated cells were also found to express mRNA specific for adipogenesis ('peroxisome proliferation-activated receptor gamma2' and lipoprotein lipase), chondrogenesis (collagen type II) and osteogenesis (osteocalcin, osteopontin and alkaline phosphatase). In conclusion, this research has successfully isolated fibroblast-like cells from human bone marrow and these cells demonstrated morphological, cytochemical and immunochemical characteristics similar to mesenchymal stem cells. These cells maintain their proliferative properties and could be differentiated into the mesoderm lineage. The success of this study is vital because mesenchymal stem cells can be used in cellular therapy to regenerate or replace damaged tissues, or as a vehicle for therapeutic gene delivery in the future.

Matched MeSH terms: Chondrocytes/cytology*; Chondrocytes/metabolism
Growth kinetic study on normal and microtic chondrocytes of human auricular cartilage

Ishak MF, Aminuddin BS, Asma A, Lokman BS, Ruszymah BH, Goh BS

Med J Malaysia, 2008 Jul;63 Suppl A:117-8.
PMID: 19025013

Chondrocytes were isolated from normal and microtic human auricular cartilage after ear surgery carried out at Universiti Kebangsaan Malaysia Medical Centre. Chondrocytes were cultured and expanded until passage 4. After reached confluence, cultured chondrocytes at each passage (P1, P2, P3 and P4) were harvested and assigned for growth profile analysis. There was no significant difference in cell viability between both normal and microtic samples (p = 0.84). Both samples showed no significant differences for growth profile parameters in terms of growth rate, population doubling time and total number of cell doubling, except in passage 1, where there is significant difference in cell growth rate (p = 0.004). This preliminary data has indicated that chondrocytes from microtic cartilage has the potential to be used in the reconstruction of human pinna in the future.

Matched MeSH terms: Chondrocytes/cytology*; Chondrocytes/physiology
Fulltext Ultrastructural changes of the articular cartilage in some arthropathies with special reference to chondrocyte cell death

Kapitonova MY, Mansor O

Malays J Pathol, 2003 Jun;25(1):15-27.
PMID: 16196374

OBJECTIVE: To determine in situ using TEM the balance of apoptosis and necrosis in the articular cartilage of patients with inflammatory (rheumatoid arthritis and seronegative spondyloarthritis) and degenerative (osteoarthritis) joint diseases and to establish possible correlation between the cell death rate and the matrix vesicles formation.
METHODS: Cartilage samples of the knee joint were obtained from patients with rheumatoid arthritis (RA, 18 cases), osteoarthritis (OA, 22 cases), Reiter's disease (RD, 9 cases), peripheral form of the ankylosing spondyloarthritis (AS, 6 cases) and psoriatic arthritis (PA, 6 cases) during arthroscopy or knee surgery. Normal samples taken from autopsy cases without a history of joint diseases were used as control. Samples were processed for TEM with subsequent semi-quantitative estimation of the cell death rate in the superficial, middle and deep zone of non-calcified articular cartilage, and computer-aided ultramorphometric evaluation of the matrix vesicles of different types.
RESULTS: Both apoptotic and necrotic cell death could be identified in the cartilage of patients with inflammatory joint diseases, including seronegative spondyloarthritides and degenerative arthropathies. Apoptosis dominated over necrosis in all examined arthritides, including RA patients in which necrosis of the chondrocyte was the most frequent among arthropathies, while the highest apoptotic cell death rate was discovered in OA in which it correlated with the volume and numeric density of the matrix vesicles. These data provide evidence that apoptosis may contribute to the cartilage breakdown not only in RA and OA but also in the seronegative spondyloarthritides, which had a significantly higher apoptotic rate than the normal cartilage.

Matched MeSH terms: Chondrocytes/pathology*; Chondrocytes/ultrastructure
The formation of human auricular cartilage from microtic tissue: An in vivo study

Ishak MF, See GB, Hui CK, Abdullah Ab, Saim Lb, Saim Ab, et al.

Int J Pediatr Otorhinolaryngol, 2015 Oct;79(10):1634-9.
PMID: 26250439 DOI: 10.1016/j.ijporl.2015.06.034

This study aimed to isolate, culture-expand and characterize the chondrocytes isolated from microtic cartilage and evaluate its potential as a cell source for ear cartilage reconstruction. Specific attention was to construct the auricular cartilage tissue by using fibrin as scaffold.

Matched MeSH terms: Chondrocytes/cytology*; Chondrocytes/metabolism
Cyclic compression of chondrocytes modulates a purinergic calcium signalling pathway in a strain rate- and frequency-dependent manner

Pingguan-Murphy B, El-Azzeh M, Bader DL, Knight MM

J Cell Physiol, 2006 Nov;209(2):389-97.
PMID: 16883605

Mechanical loading modulates cartilage homeostasis through the control of matrix synthesis and catabolism. However, the mechanotransduction pathways through which chondrocytes detect different loading conditions remain unclear. The present study investigated the influence of cyclic compression on intracellular Ca2+ signalling using the well-characterised chondrocyte-agarose model. Cells labelled with Fluo4 were visualised using confocal microscopy following a period of 10 cycles of compression between 0% and 10% strain. In unstrained agarose constructs, not subjected to cyclic compression, a subpopulation of approximately 45% of chondrocytes exhibited spontaneous global Ca2+ transients with mean transient rise and fall times of 19.4 and 29.4 sec, respectively. Cyclic compression modulated global Ca2+ signalling by increasing the percentage of cells exhibiting Ca2+ transients (population modulation) and/or reducing the rise and fall times of these transients (transient shape modulation). The frequency and strain rate of compression differentially modulated these Ca2+ signalling characteristics providing a potential mechanism through which chondrocytes may distinguish between different loading conditions. Treatment with apyrase, gadolinium and the P2 receptor blockers, suramin and basilen blue, significantly reduced the percentage of cells exhibiting Ca2+ transients following cyclic compression, such that the mechanically induced upregulation of Ca2+ signalling was completely abolished. Thus cyclic compression appears to activate a purinergic pathway involving the release of ATP followed by the activation of P2 receptors causing a combination of extracellular Ca2+ influx and intracellular Ca2+ release. Knowledge of this fundamental cartilage mechanotransduction pathway may lead to improved therapeutic strategies for the treatment of cartilage damage and disease.

Matched MeSH terms: Chondrocytes/cytology*; Chondrocytes/metabolism*

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