DCC is expressed in a CD166-positive subpopulation of chondrocytes in human osteoarthritic cartilage and modulates CRE activity

Bosserhoff, Anja-Katrin and Hofmeister, Simone and Ruedel, Anke and Schubert, Thomas (2014) DCC is expressed in a CD166-positive subpopulation of chondrocytes in human osteoarthritic cartilage and modulates CRE activity. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY, 7 (5). pp. 1947-1956. ISSN 1936-2625,

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Abstract

Objective: In a recent study we determined a strong differential expression of DCC in OA compared to normal chondrocytes and a strong impact of the DCC receptor on cellular mobility triggered by its ligand Netrin-1. Migration of chondrocytes or their progenitor cells may play a role in remodeling of cartilage and pathological conditions. The purpose of this study is to identify subsets of chondrocytes expressing DCC and to understand signaling pathways used by DCC in chondrocytes. Methods: Immunofluorescent histology of human cartilage was used to determine the expression pattern of CD166, DCC and p-CREB. Cell culture of chondrocytes and SW1353, transient transfection, siRNA transfection, EMSA, luciferase assay, quantitative RT-PCR, ELISA, and Western Blotting were used to study signaling down-stream of DCC. Results: DCC expressing chondrocytes are mainly located in the surface layers of OA cartilage. These also express CD166 indicating that DCC expressing chondrocytes are progenitor cells. Interestingly, expression of DCC reduces cAMP levels, CREB DNA-binding activity and CRE activity in chondrocytes, whereas down-regulation of DCC results in induction of CRE signaling. Conclusion: In summary, DCC is up-regulated in CD166-positive chondrogenic progenitor cells in OA and induces down-regulation of CREB. These findings indicate that migration of CD166 positive progenitor cells to sites of cartilage damage may be directed by regulation of DCC signaling.

Item Type: Article
Uncontrolled Keywords: INTERVERTEBRAL DISCS; RHEUMATOID-ARTHRITIS; CELL-PROLIFERATION; NUCLEUS PULPOSUS; AXON OUTGROWTH; MIGRATION; PROTEIN; FAMILY; CANCER; MORPHOGENESIS; Repellent factors; DCC; migration; osteoarthritis; CRE activity; CREB
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Pathologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 29 Nov 2019 08:36
Last Modified: 29 Nov 2019 08:36
URI: https://pred.uni-regensburg.de/id/eprint/10968

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