{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T11:28:43Z","timestamp":1791026923528,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2001,7,13]],"date-time":"2001-07-13T00:00:00Z","timestamp":994982400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Developmental Dynamics"],"published-print":{"date-parts":[[2001,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The formation of a secondary ossification center in the cartilaginous epiphysis of long bones requires the excavation of canals and marrow space and, therefore, the resorption of cartilage. On the assumption that its resorption requires the lysis of the major cartilage component aggrecan, it was noted that the core protein may be cleaved in vitro by proteinases from two subfamilies: matrix metalloproteinases (MMPs) and aggrecanases. Such cleavage results in aggrecan being replaced by a fragment of itself referred to as a \u201cG1\u2010fragment.\u201d To find out if this cleavage occurs in the developing epiphysis of the rat tibia, the approach has been to localize the G1 fragments. For this purpose two neoepitope antisera were applied, one capable of recognizing the MMP\u2010generated G1\u2010fragment that bears the C\u2010terminus \u2026FVDIPEN<jats:sup>341<\/jats:sup> and the other capable of recognizing the aggrecanase\u2010generated G1\u2010fragment that carries the C\u2010terminus \u2026NITEGE<jats:sup>373<\/jats:sup>. With the aid of these antisera, we report here that aggrecan cleavage is localized to newly developed sites of erosion. Thus, at 6 days of age, canals allowing the entry of capillaries are dug out from the surface of the epiphysis in a radial direction (stage I), whereas immunostaining indicative of aggrecan cleavage by MMPs appears at the blind end of each canal. The next day, the canal blind ends fuse to create a marrow space in the epiphysis (stage II), whereas immunostaining produced by MMPs occurs along the walls of this space. By 9 days, clusters of hypertrophic chondrocytes are scattered along the marrow space wall to initiate the formation of the secondary ossification center (stage III), where the resorption sites are unreactive to either antiserum. From the 9th to the 21st day, the center keeps on enlarging and, as the distal wall of the marrow space recedes, it is intensely immunostained with both antisera indicating that both MMPs and aggrecanases are involved in this resorption. We conclude, that both enzyme subfamilies contribute to the lysis of aggrecan. However, the results suggest that the respective subfamilies target different sites and even stages of development in the tissue, suggesting some diversity in the mode of aggrecan lysis during the excavation of a secondary ossification center. \u00a9 2001 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/dvdy.1168","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T16:44:49Z","timestamp":1030293889000},"page":"52-70","source":"Crossref","is-referenced-by-count":45,"title":["Enzymes active in the areas undergoing cartilage resorption during the development of the secondary ossification center in the tibiae of rats ages 0\u201321 days: I. Two groups of proteinases cleave the core protein of aggrecan"],"prefix":"10.1002","volume":"222","author":[{"given":"Eunice R.","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Lamplugh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Antonietta","family":"Davoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Beauchemin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S.","family":"Mort","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles Philippe","family":"Leblond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2001,8,7]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.33.23443"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.108.12.3649"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3330159"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0040-8166(86)90071-6"},{"key":"e_1_2_7_6_1","first-page":"1","article-title":"Are perivascular cells in cartilage canals chondrocytes?","volume":"165","author":"Cole AA","year":"1989","journal-title":"J Anat"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1001740203"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1001800304"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000146324"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3310453"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.1160"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000147177"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1159\/000147095"},{"key":"e_1_2_7_14_1","doi-asserted-by":"crossref","first-page":"17757","DOI":"10.1016\/S0021-9258(18)45444-0","article-title":"Complete primary structure of the rat cartilage proteoglycan core protein deduced from cDNA clones","volume":"262","author":"Doege K","year":"1987","journal-title":"J Biol Chem"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)35257-2"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.151.4.879"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmor.1050400302"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)48387-1"},{"key":"e_1_2_7_19_1","doi-asserted-by":"crossref","first-page":"15579","DOI":"10.1016\/S0021-9258(18)98442-5","article-title":"Cleavage of cartilage proteoglycan between G1 and G2 domains by stromelysins","volume":"266","author":"Fosang AJ","year":"1991","journal-title":"J Biol Chem"},{"key":"e_1_2_7_20_1","doi-asserted-by":"crossref","first-page":"19470","DOI":"10.1016\/S0021-9258(18)41799-1","article-title":"The interglobular domain of cartilage aggrecan is cleaved by PUMP, gelatinases, and cathepsin B","volume":"267","author":"Fosang AJ","year":"1992","journal-title":"J Biol Chem"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2950273"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(95)01539-6"},{"key":"e_1_2_7_23_1","first-page":"61","article-title":"Untersuchungen an St\u00fctzgeweben. 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