Upregulation of type X collagen expression in osteoarthritic cartilage

Mark, Klaus von der; Frischholz, Svenja; Aigner, Thomas; Beier, Frank; Belke, J; Erdmann, Silke; Burkhardt, Harald

doi:10.3109/17453679509157667

Cited by 37 publications

(21 citation statements)

References 28 publications

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“…In summary, dissection of type X collagen gene regulation during chondrocyte hypertrophy has been attempted by both in vitro and in vivo studies. Recently, this has also drawn extensive attention from scientists all over the world, because chondrocyte maturation is not only a critical stage of skeletal development but also an essential player that is involved in the pathogenesis of skeletal dysplasia and osteoarthritis (1–6) . Published results to date point to a plethora of possible transcription factors and cis ‐enhancer elements (12,13,15,37) that contribute to regulation of Col10a1 expression.…”

Section: Discussionmentioning

confidence: 99%

“…T he type X collagen gene ( Col10a1 ) is a specific molecular marker of hypertrophic chondrocytes, a terminal stage of endochondral ossification. Altered COL10A1 expression and chondrocyte hypertrophy have been associated with a spectrum of skeletal disorders such as Schmid metaphyseal chondrodysplasia (SMCD), cleidocranial dysplasia (CCD), and osteoarthritis (1–6) . It has been reported that Col10a1 ‐null mice have subtle growth plate compressions partially resembling SMCD (7) .…”

Section: Introductionmentioning

confidence: 99%

“…Altered COL10A1 expression and chondrocyte hypertrophy have been associated with a spectrum of skeletal disorders such as Schmid metaphyseal chondrodysplasia (SMCD), cleidocranial dysplasia (CCD), and osteoarthritis. (1)(2)(3)(4)(5)(6) It has been reported that Col10a1-null mice have subtle growth plate compressions partially resembling SMCD. (7) Abnormal hypertrophic cartilage and Col10a1 expression in the cranial base have also been observed in certain mouse models, suggesting its potential role in craniofacial development.…”

Section: Introductionmentioning

confidence: 99%

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Localization of the Cis-Enhancer Element for Mouse Type X Collagen Expression in Hypertrophic Chondrocytes In Vivo

Zheng

Keller

Zhou

et al. 2009

Journal of Bone and Mineral Research

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The type X collagen gene (Col10a1) is a specific molecular marker of hypertrophic chondrocytes during endochondral bone formation. Mutations in human COL10A1 and altered chondrocyte hypertrophy have been associated with multiple skeletal disorders. However, until recently, the cis-enhancer element that specifies Col10a1 expression in hypertrophic chondrocytes in vivo has remained unidentified. Previously, we and others have shown that the Col10a1 distal promoter (24.4 to 23.8 kb) may harbor a critical enhancer that mediates its tissue specificity in transgenic mice studies. Here, we report further localization of the cis-enhancer element within this Col10a1 distal promoter by using a similar transgenic mouse approach. We identify a 150-bp Col10a1 promoter element (24296 to 24147 bp) that is sufficient to direct its tissue-specific expression in vivo. In silico analysis identified several putative transcription factor binding sites including two potential activator protein-1 (AP-1) sites within its 59-and 39-ends (24276 to 24243 and 24166 to 24152 bp), respectively. Interestingly, transgenic mice using a reporter construct deleted for these two AP-1 elements still showed tissue-specific reporter activity. EMSAs using oligonucleotide probes derived from this region and MCT cell nuclear extracts identified DNA/protein complexes that were enriched from cells stimulated to hypertrophy. Moreover, these elements mediated increased reporter activity on transfection into MCT cells. These data define a 90-bp cis-enhancer required for tissuespecific Col10a1 expression in vivo and putative DNA/protein complexes that contribute to the regulation of chondrocyte hypertrophy. This work will enable us to identify candidate transcription factors essential both for skeletal development and for the pathogenesis of skeletal disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Localization of the Cis-Enhancer Element for Mouse Type X Collagen Expression in Hypertrophic Chondrocytes In Vivo

Zheng

Keller

Zhou

et al. 2009

Journal of Bone and Mineral Research

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“…Consistent with our results, Zhen et al (40) reported that parathyroid hormone inhibits type X collagen expression in hypertrophic chondrocytes by suppressing p38 pathways. Von der Mark et al (41) reported the focal appearance of type X collagen in osteoarthritic cartilage, which may be involved in the degenerative changes of the articular cartilage and in the pathogenesis of osteoarthritis. Using the mouse model of osteoarthritis, we found that activated p38 is associated with type X colla-…”

Section: Discussionmentioning

confidence: 99%

Distinct roles of Smad pathways and p38 pathways in cartilage-specific gene expression in synovial fibroblasts

Seto¹,

Kamekura²,

Miura³

et al. 2004

J. Clin. Invest.

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Nonstandard abbreviations used: anterior cruciate ligament (ACL); bone morphogenetic protein (BMP); constitutively active activin receptor-like kinase 3 (ALK3 CA ); constitutively active MKK6 (MKK6 CA ); hemagglutinin (HA); matrix metalloproteinase (MMP); medial meniscus (MM); osteoarthritis (OA); receptorregulated Smad (R-Smad); synovial fibroblast (SF); TGF-β-activating kinase 1 (TAK1). Conflict of interest:The authors have declared that no conflict of interest exists. IntroductionInjury to the articular cartilage occurs under various pathological conditions such as trauma, inflammation, and aging (1), and cartilage injury is followed by osteoarthritic changes of the affected joints. Osteoarthritis is the most common degenerative joint disorder, affecting nearly half of the elderly population. Osteoarthritis is characterized by degradation of articular cartilage and overgrowth of cartilage and bone, known as osteophytes, at the periphery of the articular surface, which results in pain and loss of joint function (1, 2). Microscopically, loss of proteoglycan and fibrillation of the articular surface are observed at the early stage of arthritis. At later stages, clefts are formed, and at the end stage, erosive changes in the articular cartilage appear. The high prevalence of this disease results in high costs for treating patients, and therefore the development of good therapeutics for osteoarthritis is a matter of great urgency. Because of the limited capacity of spontaneous healing, the regeneration of intact articular cartilage is one of the most challenging issues in the orthopedic field (3, 4). Transplantation of autologous chondrocytes or mesenchymal progenitor cells and autogenous osteochondral transplantation (mosaicplasty) have been successfully utilized for the repair of focal osteochondral defects (3, 5-11). However, the application of these technologies is limited to small defects due to the difficulty of obtaining a sufficient amount of cells or tissues. Synovium is a thin tissue lining the nonarticular surfaces of diarthrodial joints (12). Synovial tissues contain various types of cells, including type A cells, macrophage lineage cells, and type B cells, which are specialized synovial fibroblasts (SFs). It is now widely recognized that synovial tissues are involved primarily in the pathogenesis of arthritic joint disorders such as rheumatoid arthritis by producing the matrix-degenerating enzymes cystein proteases and matrix metalloproteinases (MMPs) and the proinflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) (12). We previously reported that SFs express a high level of receptor activator of NF-κB ligand, the osteoclast differentiation factor belonging to the TNF-α superfamily (13). In contrast to such catabolic actions, there is accumulating evidence that synovial cells have anabolic effects, leading to bone and cartilage production. Hunziker and Rosenburg reported that synovial cells can migrate into partial-thickness articular cartilage defects, where they prolifera...

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“…Indeed, during the development of osteoarthritis (OA), a deficit in TGFβ signalling results in chondrocyte proliferation22 and differentiation, accompanied by marker expression of the hypertrophic differentiation stage, such as alkaline phosphatase,23 type X collagen24 25 and matrix metalloproteinase 13 (MMP-13),26 with subsequent apoptotic death27 and mineralisation of the diseased cartilage 28. TGFβ1 can mediate its chondroprotective effects by binding to the activin-like kinase 5 (ALK-5) TGFβ type I/ TGFβ type II receptor heterodimer and activation of Smad2/3 signalling 29.…”

Section: Introductionmentioning

confidence: 99%

Forced exercise-induced osteoarthritis is attenuated in mice lacking the small leucine-rich proteoglycan decorin

et al. 2016

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Upregulation of type X collagen expression in osteoarthritic cartilage

Cited by 37 publications

References 28 publications

Localization of the Cis-Enhancer Element for Mouse Type X Collagen Expression in Hypertrophic Chondrocytes In Vivo

Localization of the Cis-Enhancer Element for Mouse Type X Collagen Expression in Hypertrophic Chondrocytes In Vivo

Distinct roles of Smad pathways and p38 pathways in cartilage-specific gene expression in synovial fibroblasts

Forced exercise-induced osteoarthritis is attenuated in mice lacking the small leucine-rich proteoglycan decorin

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