Ontogeny of rat chondrocyte proliferation: studies in embryo, adult and osteoarthritic (OA) cartilage

Gómez-Camarillo, Madaí A.; Kourí, Juan B.

doi:10.1038/sj.cr.7290273

Cited by 18 publications

(16 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Polysome profiling revealed that many components of ECM including fibronectin are translationally repressed in unchallenged chondrocytes despite relatively high mRNA levels. This repression is consistent with the low mitotic activity of the residing chondrocytes (49, 50). However, high mRNA abundance of Fn1 in unchallenged chondrocytes makes this gene a quick responder to different stimulus through protein abundance in OA cartilage.…”

Section: Discussionsupporting

confidence: 86%

Control of cartilage homeostasis and osteoarthritis progression by mTORC1/4E-BP/eIF4E axis

Katsara

Attur²,

Kolupaeva³

2019

Preprint

View full text Add to dashboard Cite

As world population growing older, burden of age-related conditions soars. One of them is osteoarthritis (OA), a debilitating joint disease with no effective treatment. Articular cartilage degeneration is a central event in OA, and changes in expression of many genes in OA cartilage are well-documented. Still, the specific mechanisms are rarely known. We showed that in OA cartilage the increased abundance of many proteins, including extracellular matrix protein Fibronectin (Fn1) and an orphan nuclear receptor Nr4a1 is translationally controlled and requires inactivation of 4EBP, an inhibitor of cap-dependent translation. Importantly, intra-articular injection of the translation inhibitor 4E1RCat reduces Fn1 and Nr4a upregulation in a rodent OA model and delays cartilage degeneration. Our results support the hypothesis that maintaining proper translational control is an important homeostatic mechanism, the loss of which contributes to OA development.Recent publications from two independent groups have highlighted the importance of IL-1 signaling in various small and larger animal models of posttraumatic OA (22)(23)(24)(25). For example, IL-1 receptor antagonist therapy significantly improved cartilage, synovial membrane parameters, and disease-modifying effects in the equine OA model (26). The role of translation control in the inflammatory response was examined in macrophages (27), but never in chondrocytes. We therefore used polysome profiling to assess the translational landscape of IL-1β treated primary articular chondrocytes. In polysomal profiling, actively translated mRNAs bound by several ribosomes (polysomes) are separated from "free" mRNA and the 80S monosomes by sucrose gradient centrifugation. This allows determining the translational status of a specific mRNA. Potential clinical relevance of several identified translationally controlled targets, such as Fn and an orphan receptor Nr4a1, was tested in diseased cartilage and in a rodent model of post-traumatic OA. To demonstrate the importance of translational control for cartilage homeostasis, we injected intra-articularly an inhibitor of cap-dependent translation. This treatment significantly delays OA progression. Our findings therefore reveal that translational control, acting at Fn and Nr4a1 among other targets, is essential for maintaining cartilage homeostasis.Moreover, targeting translational apparatus represents a new strategy to treat/prevent OA, particularly as it opens up the possibility to target simultaneously a pool of functionally distinct proteins. MATERIALS AND METHODSIsolation and characterization of translationally active pool of mRNAs by polysome fraction analysis, library preparation, and sequencing. RAC was isolated and treated at the first passage as described previously (18). For 10 final minutes, cells were incubated with Cyclohexamide (100ug/ml) at 37 o C.Cells were collected, washed twice with ice-cold PBS supplemented with Cyclohexamide (100ug/ml) and lysed on ice for 10min in buffer "A" (SI). 2OD units of extract (3 independ...

show abstract

Section: Discussionsupporting

confidence: 86%

Control of cartilage homeostasis and osteoarthritis progression by mTORC1/4E-BP/eIF4E axis

Katsara

Attur²,

Kolupaeva³

2019

Preprint

View full text Add to dashboard Cite

show abstract

“…The present data unquestionably raise the question of whether cellular proliferation may be responsible for the observed increase in the superficial chondrocyte numbers and the spatial remodeling of the cellular organization in early OA. Although proliferation of chondrocytes is a topic of controversy, many studies have shown that chondrocytes are in fact mitotically active (2, 26–33). In OA, fibrillation‐ or lesion‐associated cellular aggregation is thought to be related to chondrocyte proliferation (2, 10–12, 34).…”

Section: Discussionmentioning

confidence: 99%

“…In a study of advanced OA cartilage samples, the investigators doubted the existence of chondrocyte cell division and, consequently, the existence of cell proliferation in OA (33). Observing mitoses as direct evidence of proliferation, they reported the absence of mitotic figures in cartilage with advanced OA.…”

Section: Discussionmentioning

confidence: 99%

“…Observing mitoses as direct evidence of proliferation, they reported the absence of mitotic figures in cartilage with advanced OA. Nevertheless, they concluded that the induction of cell division in adult and OA cartilage remains an open subject due to the existence of factors essential for cell division (33). Most importantly, they considered chondrocyte proliferation to be likely in early OA (33).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Proliferative remodeling of the spatial organization of human superficial chondrocytes distant from focal early osteoarthritis

Rolauffs

Williams

Aurich

et al. 2010

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. Human superficial chondrocytes show distinct spatial organizations, and they commonly aggregate near osteoarthritic (OA) fissures. The aim of this study was to determine whether remodeling or destruction of the spatial chondrocyte organization might occur at a distance from focal (early) lesions in patients with OA.Methods. Samples of intact cartilage (condyles, patellofemoral groove, and proximal tibia) lying distant from focal lesions of OA in grade 2 joints were compared with location-matched nondegenerative (grade 0-1) cartilage samples. Chondrocyte nuclei were stained with propidium iodide, examined by fluorescence microscopy, and the findings were recorded in a top-down view. Chondrocyte arrangements were tested for randomness or significant grouping via point pattern analyses (Clark and Evans Aggregation Index) and were correlated with the OA grade and the surface cell densities.Results. In grade 2 cartilage samples, superficial chondrocytes were situated in horizontal patterns, such as strings, clusters, pairs, and singles, comparable to the patterns in nondegenerative cartilage. In intact cartilage samples from grade 2 joints, the spatial organization included a novel pattern, consisting of chondrocytes that were aligned in 2 parallel lines, building double strings. These double strings correlated significantly with an increased number of chondrocytes per group and an increased corresponding superficial zone cell density. They were observed in all grade 2 condyles and some grade 2 tibiae, but never in grade 0-1 cartilage.Conclusion. This study is the first to identify a distinct spatial reorganization of human superficial chondrocytes in response to distant early OA lesions, suggesting that proliferation had occurred distant from focal early OA lesions. This spatial reorganization may serve to recruit metabolically active units as an attempt to repair focal damage.

show abstract

“…Proliferation of chondrocytes has been suggested as the principal mechanism in cluster formation based on studies of 3 H-thymidine and/or bromodeoxyuridine incorporation and the detection of proliferation markers such as PCNA and Ki67 in experimental OA models [53,54]. Because mitotic figures have not been detected in either mature or OA articular cartilage [53], chondrocyte migration has been suggested as a contributor to cluster formation. Chondrocytes have the ability to migrate in vitro in response to cytokines and growth factors [55,56].…”

Section: Discussionmentioning

confidence: 98%

Menisectomized miniature Vietnamese pigs develop articular cartilage pathology resembling osteoarthritis

Cruz

Rojas

et al. 2015

Pathology - Research and Practice

View full text Add to dashboard Cite

Ontogeny of rat chondrocyte proliferation: studies in embryo, adult and osteoarthritic (OA) cartilage

Cited by 18 publications

References 37 publications

Control of cartilage homeostasis and osteoarthritis progression by mTORC1/4E-BP/eIF4E axis

Control of cartilage homeostasis and osteoarthritis progression by mTORC1/4E-BP/eIF4E axis

Proliferative remodeling of the spatial organization of human superficial chondrocytes distant from focal early osteoarthritis

Menisectomized miniature Vietnamese pigs develop articular cartilage pathology resembling osteoarthritis

Contact Info

Product

Resources

About