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286534 occurrences (No.87 in the rank) during 5 years in the PubMed. [no cache] 500 found

304) A participation of extracellular, isolated chondrocalcin in mineralization was proposed more than 25 years ago, but never demonstrated.

--- ABSTRACT ---

PMID:23851124 DOI:10.1016/j.matbio.2013.06.002

2015 Matrix biology : journal of the International Society for Matrix Biology

* Chondrocalcin is internalized by chondrocytes and triggers cartilage destruction via an interleukin-1β-dependent pathway.

- Chondrocalcin is among the most highly synthesized polypeptides in cartilage. This protein is released from its parent molecule, type II pro-collagen, after secretion by chondrocytes. A participation of extracellular, isolated chondrocalcin in mineralization was proposed more than 25 years ago, but never demonstrated. Here, exogenous chondrocalcin was found to trigger MMP13 secretion and cartilage destruction ex vivo in human cartilage explants and did so by modulating the expression of interleukin-1β in primary chondrocyte cultures in vitro. Chondrocalcin was found internalized by chondrocytes. Uptake was found mediated by a single 18-mer peptide of chondrocalcin, which does not exhibit homology to any known cell-penetrating peptide. The isolated peptide, when artificially linked as a tetramer, inhibited gene expression regulation by chondrocalcin, suggesting a functional link between uptake and gene expression regulation. At the same time, the tetrameric peptide potentiated chondrocalcin uptake by chondrocytes, suggesting a cooperative mechanism of entry. The corresponding peptide from type I pro-collagen supported identical cell-penetration, suggesting that this property may be conserved among C-propeptides of fibrillar pro-collagens. Structural modeling localized this peptide to the tips of procollagen C-propeptide trimers. Our findings shed light on unexpected function and mechanism of action of these highly expressed proteins from vertebrates.

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[frequency of next (right) word to demonstrated]

(1)158 that	(10)5 good	(19)3 excellent	(28)2 efficacy
(2)48 the	(11)5 increased	(20)3 more	(29)2 greater
(3)40 a	(12)5 significantly	(21)3 no	(30)2 how
(4)23 by	(13)4 as	(22)3 that,	(31)2 successful
(5)21 to	(14)4 better	(23)2 acceptable	(32)2 through
(6)13 in	(15)4 improved	(24)2 and	(33)2 using
(7)12 null	(16)4 its	(25)2 both
(8)11 an	(17)4 similar	(26)2 decreased
(9)8 for	(18)3 between	(27)2 differential

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--- WordNet output for demonstrated --- Overview of verb demonstrate The verb demonstrate has 4 senses (first 4 from tagged texts) 1. (24) show, demo, exhibit, present, demonstrate -- (give an exhibition of to an interested audience; "She shows her dogs frequently"; "We will demo the new software in Washington") 2. (22) prove, demonstrate, establish, show, shew -- (establish the validity of something, as by an example, explanation or experiment; "The experiment demonstrated the instability of the compound"; "The mathematician showed the validity of the conjecture") 3. (2) attest, certify, manifest, demonstrate, evidence -- (provide evidence for; stand as proof of; show by one's behavior, attitude, or external attributes; "His high fever attested to his illness"; "The buildings in Rome manifest a high level of architectural sophistication"; "This decision demonstrates his sense of fairness") 4. (1) demonstrate, march -- (march in protest; take part in a demonstration; "Thousands demonstrated against globalization during the meeting of the most powerful economic nations in Seattle") Overview of adj demonstrated The adj demonstrated has 1 sense (first 1 from tagged texts) 1. (1) demonstrated -- (having been demonstrated or verified beyond doubt) --- WordNet end ---