Molecular differentiation in epiphyseal and physeal cartilage. Prominent role for gremlin in maintaining hypertrophic chondrocytes in epiphyseal cartilage.
We have studied hypertrophic and immediately adjacent pre-hypertrophic chondrocytes at the same stage of histologic development in 7 day old post-natal Balb/C mouse physes and epiphyses. Laser capture microdissection (LCM) and GeneChip microarray analysis compared the molecular composition of the two hypertrophic chondrocyte regions. Molecules upregulated in dramatically higher levels in the epiphysis were gremlin (58-fold), epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (25-fold), and frizzled related protein (6.4-fold and 5.7-fold). Molecules upregulated in higher levels in the physis were proline arginine-rich end leucine-rich repeat protein (PRELP) (15.6-fold), pyrophosphatase (inorganic) 1 (10-fold) and hedgehog-interacting protein (7.3-fold). Immunocytochemistry for gremlin confirmed specific localization patterns. This study indicates a critical site-specific role for hypertrophic chondrocytes with different synthesis patterns in separate regions even though they appear structurally the same and are at the same stage of development.
Shapiro
Frederic
F
Department of Orthopaedic Surgery, Children's Hospital Boston and Harvard Medical School, Boston, MA 02115, USA. frederic.shapiro@childrens.harvard.edu
Flynn
Evelyn
E
Calicchio
Monica L
ML
D000818:Animals; D002454:Cell Differentiation; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D006023:Glycoproteins / Q000096:biosynthesis; D006132:Growth Plate / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D011506:Proteins / Q000378:metabolism; D015854:Up-Regulation; D000099274:Frizzled-Related Proteins; D016207:Cytokines
D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D000099274:Frizzled-Related Proteins; C490748:Prelp protein, mouse; C113178:Grem1 protein, mouse; D016207:Cytokines