Ucma--A novel secreted factor represents a highly specific marker for distal chondrocytes.
Growth and development of most parts of the vertebrate skeleton takes place by endochondral ossification, a process during which chondrocytes undergo distinct stages of differentiation resulting in a successive replacement of the cartilage anlagen by bone. In the context of an EST project we isolated a novel transcript from a human fetal growth plate cartilage cDNA library. The transcript which we called Ucma (unique cartilage matrix-associated protein) encodes a short protein of 138 amino acids. The protein sequence is evolutionary conserved throughout vertebrates and comprises a signal peptide, a coiled-coil domain, and a putative dibasic cleavage site for proprotein convertases. Using RNA in situ hybridization and immunohistochemistry with a polyclonal anti-Ucma antibody we found high expression of Ucma uniquely in distal (resting) chondrocytes in developing long bones of wildtype mice. This restricted expression could also be observed in Ihh(-/-), Ihh(-/-); Gli3(-/-), Gli3(-/-) mice, and in mice that overexpress Ihh under the control of the Col2a1 promoter indicating that expression of Ucma is regulated independent of hedgehog signaling. During insulin-induced differentiation of ATDC5 cells we found gradual increase of Ucma expression at day 21 with a maximum at day 24 and a decrease correlating with a simultaneous increase in the expression of cartilage link protein (Crtl1), a protein with maximum expression in column-forming proliferating chondrocytes. The present data strongly suggest an important function of Ucma in the early phase of chondrocyte differentiation.
Tagariello
Andreas
A
Institute of Human Genetics, University Hospital Erlangen, Schwabachanlage 10, D-91054 Erlangen, Germany.
Luther
Julia
J
Streiter
Melanie
M
Didt-Koziel
Lydia
L
Wuelling
Manuela
M
Surmann-Schmitt
Cordula
C
Stock
Michael
M
Adam
Nadia
N
Vortkamp
Andrea
A
Winterpacht
Andreas
A
D000595:Amino Acid Sequence; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D002358:Cartilage, Articular / Q000166:cytology / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D019902:Chondrocytes / Q000737:chemistry* / Q000166:cytology / Q000502:physiology*; D020219:Chondrogenesis / Q000502:physiology; D016326:Extracellular Matrix Proteins; D005121:Extremities / Q000033:anatomy & histology / Q000196:embryology / Q000502:physiology; D005333:Fetus / Q000033:anatomy & histology; D006132:Growth Plate / Q000166:cytology*; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D000074290:Zinc Finger Protein Gli3
D015415:Biomarkers; D016326:Extracellular Matrix Proteins; C465571:Gli3 protein, mouse; D053823:Hedgehog Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D011506:Proteins; C528959:Ucma protein, human; C528958:Ucma protein, mouse; D000074290:Zinc Finger Protein Gli3; C514061:ihh protein, mouse