Identification of a Prg4‐Expressing Articular Cartilage Progenitor Cell Population in Mice. Issue 5 (May 2015)

• Record Type: Journal Article
• Authors: Kozhemyakina, Elena; Zhang, Minjie; Ionescu, Andreia; Ayturk, Ugur M.; Ono, Noriaki; Kobayashi, Akio; Kronenberg, Henry; Warman, Matthew L.; Lassar, Andrew B.
• Is Part Of: Arthritis & rheumatology. Volume 67:Issue 5(2015)
• Page Start: 1261
• Page End: 1273
• Publication Date: 2015-05
• Subjects: Arthritis -- Periodicals; Rheumatism -- Periodicals; 616.72
• DOI: 10.1002/art.39030
• Languages: English
• ISSNs: 2326-5191

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="art39030-sec-0001" sec-type="section"> <title>Objective</title> <p>To generate knockin mice that express a tamoxifen‐inducible Cre recombinase from the <italic>Prg4</italic> locus (<italic>Prg4<sup>GFPCreERt2</sup></italic> mice) and to use these animals to fate‐map the progeny of <italic>Prg4</italic>‐positive articular cartilage cells at various ages.</p> </sec> <sec id="art39030-sec-0002" sec-type="section"> <title>Methods</title> <p>We crossed <italic>Prg4<sup>GFPCreERt2</sup></italic> mice with <italic>Rosa26<sup>floxlacZ</sup></italic> or <italic>Rosa26<sup>mTmG</sup></italic> reporter strains, admin‐istered tamoxifen to the double heterozygous offspring at different ages, and assayed Cre‐mediated recom‐bination by histochemistry and/or fluorescence microscopy.</p> </sec> <sec id="art39030-sec-0003" sec-type="section"> <title>Results</title> <p>In 1‐month‐old mice, the expression of the <italic>Prg4<sup>GFPCreERt2</sup></italic> allele mirrored the expression of endogenous <italic>Prg4</italic> and, when tamoxifen was admin‐istered for 10 days, caused Cre‐mediated recombination in ∼70% of the superficial‐most chondrocytes. <italic>Prg4<sup>GFPCreERt2</sup></italic>‐expressing cells were mostly confined to the top 3 cell layers of the articular cartilage in 1‐month‐old mice, but descendants of these cells were located in deeper regions of the articular cartilage in aged mice. On embryonic day 17.5, <italic>Prg4<sup>GFPCreERt2</sup></italic>‐expressing cells were largely restricted to the superficial‐most cell layer of the forming joint, yet at ∼1 year, the progeny of these cells spanned the depth of the articular cartilage.</p> </sec> <sec id="art39030-sec-0004" sec-type="section"> <title>Conclusion</title> <p>Our results suggest that <italic>Prg4</italic>‐expressing cells located at the joint surface in the embryo serve as a progenitor population for all deeper layers of the mature articular cartilage. Also, our findings indicate that <italic>Prg4<sup>GFPCreERt2</sup></italic> is expressed by superficial chondrocytes in young mice, but expands into deeper regions of the articular cartilage as the animals age. The <italic>Prg4<sup>GFPCreERt2</sup></italic> allele should be a useful tool for inducing efficient Cre‐mediated recombination of loxP‐flanked alleles at sites of <italic>Prg4</italic> expression.</p> </sec> </abstract>