Gene Expression Profiling of Mouse Articular and Growth Plate Cartilage

Yamane, Shintaro; Cheng, Ewana; You, Zongbing; Reddi, A. Hari

doi:10.1089/ten.2006.0431

Cited by 36 publications

(46 citation statements)

References 29 publications

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“…Expression profile studies have shown that articular chondrocytes express EPCR (in the mouse [28]) and TM (in the rat [29]), with TM also being increased in surgically induced OA in the rat. The results of the present study extend these previous observations to show the expression of protein C, EPCR, and TM in both human and ovine articular chondrocytes.…”

Section: Discussionmentioning

confidence: 99%

Activation of cartilage matrix metalloproteinases by activated protein C

Jackson

Smith

et al. 2009

Arthritis & Rheumatism

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Objective. To investigate the role of activated protein C (APC) in cartilage degradation.Methods. Chondrocyte expression of protein C, endothelial protein C receptor (EPCR), and thrombomodulin (TM) were evaluated by reverse transcriptionpolymerase chain reaction (RT-PCR). APC was immunolocalized in developing joints and in osteoarthritic (OA) cartilage from humans. The effect of APC on aggrecan and collagen degradation was examined in explant cultures of ovine cartilage in control cultures and in cultures stimulated with interleukin-1␣ (IL-1␣), tumor necrosis factor ␣ (TNF␣), or retinoic acid (RetA), using colorimetric assays and Western blotting. Chondrocyte expression of matrix metalloproteinases (MMPs), ADAMTS, and tissue inhibitor of metalloproteinases (TIMPs) was measured by RT-PCR. MMP-2 and MMP-9 activity was evaluated by gelatin zymography and MMP-13 by fluorogenic assay.Results. Positive cellular immunostaining for APC was found at sites of MMP activity in developing joints and in OA, but not normal, cartilage. Chondrocytes expressed messenger RNA for protein C, EPCR, and TM, with the latter 2 levels increased by IL-1␣ and TNF␣ stimulation. APC augmented aggrecan release and initiated collagen breakdown in IL-1␣-treated and TNF␣-treated cartilage, but not in normal or in RetAtreated cartilage. APC-stimulated aggrecan and collagen breakdown were due to MMP activity but were not associated with modulation of MMP, ADAMTS, or TIMP expression. APC resulted in MMP-13 activation in cartilage cultures. APC could not directly activate proMMP-13, but it was associated with increased MMP-2 and MMP-9 activity.Conclusion. APC may be a relevant activator of MMPs in cartilage and may play a role in progressive cartilage degradation in arthritis.

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Section: Discussionmentioning

confidence: 99%

Activation of cartilage matrix metalloproteinases by activated protein C

Jackson

Smith

et al. 2009

Arthritis & Rheumatism

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“…B то же время содержание аггрекана в этой зоне ниже, чем в дру-гих. Она богата регуляторными молекулами, такими как ТФР β1 и 3, и белками морфогенеза кости (БМК) 1-6 [41,42]. Пролиферативный потенциал клеток этого слоя опре-деляется экспрессией циклина D2.…”

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“…Пролиферативный потенциал клеток этого слоя опре-деляется экспрессией циклина D2. Однако деление может ингибироваться специфическими генами Gas1 и GADD45α, которые здесь также обнаружены [42]. Это мо-жет служить объяснением сложности выявления пролифе-ративной активности путем окрашивания на PCNA (ядер-ный антиген пролиферирующих клеток) [43].…”

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“…Зональная экспрессия генов и соответствующих им белков в ростковой пластинке Хондроциты резервной зоны очень слабо делятся, о чем свидетельствует низкая экспрессия РСNA-антигена [42]. Они производят много ВКМ, который преимущест-венно состоит из коллагена 2-го типа и аггрекана.…”

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“…Они производят много ВКМ, который преимущест-венно состоит из коллагена 2-го типа и аггрекана. Между тем в нем также присутствуют коллагены 6, 9 и 11-го ти-пов, связующий (link) белок и малые, обогащенные лей-цином протеогликаны (SLRP), такие как декорин и фиб-ромодулин [42]. В данной зоне также наблюдали экспрес-сию ряда регуляторных ростовых факторов, таких как БМК 3, 5, 7 и ТФР β1-3 [41,42,[68][69][70].…”

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MEKhANIZMY EMBRIOGENEZA PRI OSTEOARTROZE:ROL' DIFFERENTsIROVKI KhONDROTsITOVV REZORBTsII SUSTAVNOGO KhRYaShchA

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Toward regeneration of articular cartilage

Iwamoto

Ohta

Larmour

et al. 2013

Birth Defects Research Pt C

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Articular cartilage is classified into permanent hyaline cartilage and has significant differences in structure, extracelluar matrix components, gene expression profile, and mechanical property from transient hyaline cartilage found in growth plate. In the process of synovial joint development, articular cartilage is originated from the interzone, developing at the edge of the cartilaginous anlagen, it establishes zonal structure over time and supports smooth movement of the synovial joint through life. The cascade actions of key regulators such as Wnts, GDF5, Erg, and PTHLH coordinate sequential steps of articular cartilage formation. Articular chondrocytes are restrictedly controlled not to differentiate into a hypertrophic stage by autocrine and paracrine factors and extracerllular matrix microenvironment, but retain potential to undergo hypertrophy. The basal calcified zone of articular cartilage is connected with subchondral bone, but not invaded by blood vessels nor replaced by bone, which is highly contrasted with the growth plate. Articular cartilage has limited regenerative capacity, but likely possesses and potentially uses intrinsic stem cell source in the superficial layer, Ranvier’s groove, the intra-articular tissues such as synovium and fat pad, and marrow below the subchondral bone. Considering the biological views on articular cartilage, several important points are raised for regeneration of articular cartilage. We should evaluate the nature of regenerated cartilage as permanent hyaline cartilage and not just hyaline cartilage. We should study how a hypertrophic phenotype of transplanted cells can be lastingly suppressed in regenerating tissue. Further, we should develop the methods and reagents to activate recruitment of intrinsic stem/progenitor cells into the damaged site.

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Gene Expression Profiling of Mouse Articular and Growth Plate Cartilage

Cited by 36 publications

References 29 publications

Activation of cartilage matrix metalloproteinases by activated protein C

Activation of cartilage matrix metalloproteinases by activated protein C

MEKhANIZMY EMBRIOGENEZA PRI OSTEOARTROZE:ROL' DIFFERENTsIROVKI KhONDROTsITOVV REZORBTsII SUSTAVNOGO KhRYaShchA

Toward regeneration of articular cartilage

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