Cartilage biology and pathology

  • Cartilage derived retinoic acid sensitive protein (CD-RAP) as an in vitro and in vivo marker of cartilage synthesis
  • Cartilage development - role of retinoic acid, CD-RAP, and retinoic acid receptors (RAR/RXR)
  • Cartilage variations between joints - effect of impact and inflammation

Equine cartilage-derived retinoic acid-sensitive protein (CD-RAP) / melanoma inhibitory activity protein (MIA)


Aim: To provide a molecular description of equine CD-RAP/MIA, and to evaluate equine CD-RAP/MIA as a marker in vitro and in vivo.

Short description: CD-RAP/MIA is a novel cartilage protein. It is unique in that it is only expressed in cartilage and malignant melanomas, and contrary to established cartilage markers such as collagen type 2 and aggrecan CD-RAP/MIA is not a structural part of the extracellular matrix, but it is secreted into the extracellular space, where it is readily available for analysis either in the synovial fluid or serum, or in a laboratory setting also in the culture medium. The expression of CD-RAP/MIA is linked to synthesis and anabolic processes. This project is focused on establishing equine CD-RAP/MIA as a cartilage marker. The different parts of the project include a molecular description of equine CD-RAP/MIA (published in 2007), effect of dedifferentiation of chondrocytes on CD-RAP/MIA expression, evaluation of the role of CD-RAP/MIA on chondrogenic redifferentiation in mature chondrocytes (data available in thesis), CD-RAP/MIA as a marker of chondrogenic potential in a comparative study between equine mesenchymal stem cells from different tissue sources (published in part in 2009, work ongoing), and CD-RAP/MIA expression in healthy and diseased joints in horses (published in 2007).

Main investigator: Lise C. Berg
Collaborators / co-authors: Preben D. Thomsen, Xavier Mata, Stine Jacobsen, Johan Lenz, Dean H. Betts, Thomas G. Koch, Tammy Herkens, Kirill Besonov, Mads Kjelgaard-Hansen

Selected publications:
Molecular characterization and chromosomal assignment of equine cartilage derived retinoic acid sensitive protein (CD-RAP)/melanoma inhibitory activity (MIA). Berg LC, Mata X, Thomsen PD. Gene. 2008 Jan 15;407(1-2):98-104. PubMed

Cartilage-derived retinoic acid-sensitive protein in equine synovial fluid from healthy and diseased joints. Berg LC, Lenz J, Kjelgaard-Hansen M, Thomsen PD, Jacobsen S. Equine Vet J. 2008 Sep;40(6):553-7. PubMed

Chondrogenic potential of mesenchymal stromal cells derived from equine bone marrow and umbilical cord blood.  Berg LC, Koch TG, Heerkens T, Besonov K, Thomsen PD, Betts DH. Vet Comp Orthop Trauma. 2009;22(5):363-370. Schattauer

Cartilage development - the role of cartilage-derived retinoic acid-sensitive protein (CD-RAP), retinoic acid, and retinoic acid receptor (RAR/RXR) (Post Doc)


Aim: To investigate the role of CD-RAP/MIA in cartilage development, and to establish the interactions of CD-RAP/MIA, retinoic acid, and RAR in the initiation and termination of chondrogenesis.

Short description: In this study, the role of CD-RAP/MIA in cartilage development will be investigated using a model of mesenchymal stem cells and 2D and 3D cell differentiation protocols. The culture system will be adjusted to reveal potential roles and interactions between CD-RAP/MIA, retinoic acid, and RAR/RXR during the different phases of chondrogenesis. A more thorough understanding of chondrogenesis and early cartilage development will help us in the study of cartilage degeneration and repair / regeneration.

Main investigator: Lise C. Berg


The development of cartilage starts with stem cells and through the actions of biochemical and physical factors the cells condense, start to produce matrix, and mature cartilage is produced. In areas like the articular surfaces of the joints the tissue remains cartilage, but in other parts of the body, e.g. the skeleton, the process continues and the cartilage is converted into bone. Figure by L. C. Berg.

Cartilage and its response to traumatic injury and inflammation - differences between eight major articular joints


Aim: To study the variation between equine articular cartilage from eight different joints (in collaboration with Dr. Lisa Fortiers group at Cornell University)

Investigators: Kira D. Novakofski, Lise C. Berg, Ilaria Bronzini, Lisa A. Fortier

Publication:
Joint-dependent response to impact and implications for post-traumatic osteoarthritis. Novakofski KD, Berg LC, Bronzini I, Bonnevie ED, Poland SG, Bonassar LJ, Fortier LA. Osteoarthritis Cartilage. 2015 Feb 25. [Epub ahead of print]. PubMed