Distribution of type X collagen mRNA in normal and osteoarthritic human cartilage

Hoyland, Judith A.; Thomas, Jack; Donn, Rachelle; Marriott, Anna; Ayad, Shirley; Boot-Handford, Ray; Grant, Michael E.; Freemont, Anthony J.

doi:10.1016/0169-6009(91)90005-k

Cited by 125 publications

(76 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It has also been 416 STOKES ET AL shown that chondrocytes within the deep zones of OA cartilage can express type X collagen, indicating that they may be undergoing hypertrophy (8,9,72,73). Others have observed the synthesis by OA chondrocytes of aggrecan molecules that resemble the structure of aggrecan molecules in fetal chondrocytes (11).…”

Section: Discussionmentioning

confidence: 99%

“…These changes in the biosynthetic profile of dedifferentiated chondrocytes resemble some of the phenotypic changes displayed by OA chondrocytes, and the matrix they produce is similar to that synthesized by chondroprogenitor cells (7)(8)(9)(10)(11)(12)(13)17,(37)(38)(39)(40). However, the mechanisms responsible for the phenotypic instability of chondrocytes and the regulation of these different chondrocyte-specific phenotypes remain poorly understood.…”

mentioning

confidence: 92%

“…The chondro-cyte response may lead, in certain situations, to longterm changes in the phenotype of the cell, and therefore to an inability to properly repair or maintain the cartilage ECM (4). This is exemplified by the phenotypic changes in the patterns of production or in the temporal or spatial distribution of the synthesis of interstitial collagens, fibroblast-type proteoglycans, and production of ECM proteins associated with fetal development that occur during the development of osteoarthritis (OA), dedifferentiation in culture, or in response to certain types of cartilage injury (6)(7)(8)(9)(10)(11)(12)(13).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Assessment of the gene expression profile of differentiated and dedifferentiated human fetal chondrocytes by microarray analysis

Stokes¹,

Liu²,

Coimbra³

et al. 2002

Arthritis & Rheumatism

152

106

View full text Add to dashboard Cite

Objective. To study the changes in patterns of gene expression exhibited by human chondrocytes as they dedifferentiate into fibroblastic cells in culture in order to better understand the mechanisms that control this process and its relationship to the phenotypic changes that occur in chondrocytes during the development of osteoarthritis (OA).Methods. Human fetal epiphyseal chondrocytes (HFCs) were cultured either on poly-(2-hydroxyethyl methacrylate)-coated plates (differentiated HFC cultures) or in plastic tissue culture flasks as monolayers (dedifferentiated HFC cultures). Following 11 days of culture under either condition, poly(A؉) RNA was isolated from the two cell populations and subjected to a gene expression analysis using a microarray containing ϳ5,000 known human genes and ϳ3,000 expressed sequence tags (ESTs).Results. A >2-fold difference in the expression of 62 known genes and 6 ESTs was observed between the two cell types. The differences in expression of several of the genes detected by the microarray hybridization were confirmed by Northern analyses. Two transcription factor genes, TWIST and HIF-1␣, and a cellular adhesion protein gene, cadherin 11, were markedly regulated in response to differentiation and dedifferentiation. Expression of these genes was also detected in adult normal and OA cartilage and chondrocytes. Analysis of the gene expression profile of HFCs revealed a complex pattern of gene expression, including many genes not yet reported to be expressed by chondrocytes.Conclusion. Chondrocytes in monolayer become dedifferentiated, acquiring a fibroblast-like appearance and changing their pattern of gene expression from one of expression of chondrocyte-specific genes to one that resembles a fibroblastic or chondroprogenitor-like pattern. Changes in gene expression associated with the process of dedifferentiation of HFCs in vitro were observed in a wide variety of genes, including genes encoding extracellular matrix proteins, transcription factors, and growth factors. At least 3 of the genes that were regulated in response to dedifferentiation were also found to be expressed in adult normal and OA articular cartilage and chondrocytes.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 92%

mentioning

confidence: 99%

See 1 more Smart Citation

Assessment of the gene expression profile of differentiated and dedifferentiated human fetal chondrocytes by microarray analysis

Stokes¹,

Liu²,

Coimbra³

et al. 2002

Arthritis & Rheumatism

152

106

View full text Add to dashboard Cite

show abstract

“…No collagen X mRNA or protein was detectable in normal age and sex matched femoral heads. These data provided the first definitive evidence that osteoarthritic chondrocytes are stimulated to produce type X collagen and that new bone formation in OA joints is at least in part initiated by local changes in chondrocyte metabolism (Hoyland et al 1991).…”

Section: Collagen X Genes Human Diseases and Animal Modelsmentioning

confidence: 82%

Fell–Muir Lecture: From collagen chemistry towards cell therapy – a personal journey

Grant

2007

Int J Experimental Path

View full text Add to dashboard Cite

SummaryThe Fell-Muir Award requires the recipient to deliver a lecture and a review manuscript which provides a personal overview of significant scientific developments in the field of matrix biology over the period of the recipient's career. In this context, this review considers the collagen family of structural proteins and the advances in biochemical, molecular biological and genetic techniques which led to the elucidation of the structure, synthesis and function of this important group of extracellular matrix constituents. Particular attention is focussed on early research on the identification and assembly of the soluble precursors of collagen types I and II, and the identification of the precursor of basement membrane collagen type IV. In subsequent studies investigating the maintenance of the chick chondrocyte phenotype in culture, the influence of the extracellular milieu was found to influence markedly both cell morphology and collagen gene expression. These studies led to the discovery of collagen type X whose expression is restricted to hypertrophic chondrocytes at sites of endochondral ossification. Such research provided a prelude to investigations of mammalian endochondral ossification which is known to be aberrant in a variety of human chondrodysplasias and is reactivated in bone fracture repair and in osteoarthritis. The cloning of bovine and then human collagen type X genes facilitated studies in relevant human diseases and contributed to the discovery of mutations in the COL10A1 gene in families with metaphyseal chondrodysplasia type Schmid. Clustering of mutations in the C-terminal domain of the type X collagen molecule has now been widely documented and investigations of the pathogenic mechanisms in animal models are beginning to suggest the prospect of novel treatment strategies.

show abstract

“…COL-X localization and transient expression at sites of calcification suggest that it is associated with events in early stages of endochondral bone formation. COL-X gene expression was detected in chondrocytes present in OA tissue in that area where there appeared to be a re-initiation of the endochondral bone formation process including osteophytes and in the areas of subchondral bone sclerosis [69]. COL-X was present in hypertrophic chondrocytes in the vertebrae of P1 spine ( Figure 11C).…”

Section: Type X Collagen (Col-x)mentioning

confidence: 89%

A Less Invasive Approach of Medial Meniscectomy in Rat: A Model to Target Early or Less Severe Human Osteoarthritis

Juneja¹,

Ventura²,

Jay³

et al. 2016

J Arthritis

View full text Add to dashboard Cite

Objectives: The existing medial meniscectomy (MMx) procedure in rodents involves transection of MCL and wide opening of the knee capsule followed by meniscus transection that results into articular cartilage degeneration and causes significant changes in subchondral bone at specific post-MMx period. These animals serve as experimental osteoarthritis (OA) models.Structurally, knee is very complex. There may be a need to uncouple articular cartilage degenerative changes from subchondral bone degenerative changes in experimental OA models. Therapeutical drugs/agents, designed to treat articular cartilage degenerative changes of OA knee, may not be effective to treat subchondral bone degenerative changes or vice versa.The purpose of the study was to modify the existing MMx procedure to a less invasive procedure so that it causes only articular cartilage degenerative OA changes and no subchondral bone changes. This will serve as an early OA model to target degenerative changes in articular cartilage in human.Methods: Ten 8-9 weeks old male athymic nude rats underwent less invasive MMx on right knee; the left knee served as unoperated control. The surgery involved no transection of MCL and opening of knee capsule wide. The medial meniscus was pulled out from a slit made on the medial aspect of the knee capsule, and was transected. At 10 weeks post-MMx, animals were sacrificed and knees were assessed. Results:There was no significant alteration in bone strength parameters (BV/TV, Tb.Th, Tb.Sp, Tb.N, Tb.Pf, cortical wall thickness) in subchondral bone in the less invasive MMx knee as analyzed by μCT. X-ray radiography did not indicate the presence of any osteophyte at the knee margins. On the other hand, the less invasive MMx caused degenerative changes in articular cartilage as follows: fibrillation and thinning in the medial tibia; narrowing of medial knee joint; reduced proteoglycans shown by safranin-O staining; decreased metachromasia by PSR staining; alteration in collagen fibril thickness under cross-polarization light. Immunohistochemical expression was reduced (COL-II, aggrecan), increased (NITEGE, Col2-3/4m, COL-X, and MMP13) or imbalanced (lubricin) in articular cartilage thickness of less invasive MMx knee. Conclusion:The less invasive MMx procedure, in rat, can be a model for early or less severe human OA due to articular cartilage degenerative changes only and with no subchondral bone degenerative changes in the knee synovial joint. The therapeutical drugs/agents designed to repair articular cartilage may be suitable for this model and may lead to treatment of early or less severe human OA.Citation: Juneja SC, Ventura M, Jay GD, Veillette C (2016) A Less Invasive Approach of Medial Meniscectomy in Rat: A Model to Target Early or Less Severe Human Osteoarthritis. J Arthritis 5: 193. doi:10.4172/2167-7921.1000193 Page 2 of 17 In rat and mouse, MMx surgery is usually conducted first by transecting the medial collateral ligament (MCL) fully or partially followed by wide opening of the knee capsule, ...

show abstract

Distribution of type X collagen mRNA in normal and osteoarthritic human cartilage

Cited by 125 publications

References 25 publications

Assessment of the gene expression profile of differentiated and dedifferentiated human fetal chondrocytes by microarray analysis

Assessment of the gene expression profile of differentiated and dedifferentiated human fetal chondrocytes by microarray analysis

Fell–Muir Lecture: From collagen chemistry towards cell therapy – a personal journey

A Less Invasive Approach of Medial Meniscectomy in Rat: A Model to Target Early or Less Severe Human Osteoarthritis

Contact Info

Product

Resources

About