Applicant

 Name: Univ.-Prof. Dr. Arndt F. Schilling

 E-mail: arndt.schilling@med.uni-goettingen.de


Cartilage Adjacent Subchondral Bone (CASB) in ageing and disease as a diagnostic and therapeutic target

Careful evaluation of animal experimental data of osteoarthritis (OA) has revealed that changes in the subchondral bone structure precede the loss of cartilage. These results suggest that the increased bone mass in the subchondral zone may also be a cause rather than only an effect of OA. In this project we will specifically study at ultra-high resolution the zone between the cartilage and the spongy bone consisting of tidemark, calcified cartilage and subchondral bone, which we will term cartilage adjacent subchondral bone (CASB). In healthy joints, this complicated structure is reported to gradually relay impacting forces from the soft cartilage to the hard spongy bone.

 

Our working hypothesis is that the three-dimensional nano-architecture of the cartilage adjacent subchondral bone (CASB), changes during the development of OA. We further hypothesize that these changes play an important role in the development of osteoarthritis and can be utilized for the development of early diagnostic tools, for the monitoring of treatment and the development of novel therapeutic strategies.

 

Consequently, our main objective is it to investigate the 3D-nano-architecture of the CASB in healthy and osteoarthritic samples, correlate observed changes in the bone to changes in the cartilage and develop theories to explain our findings and propose novel diagnostics and treatment modalities.

 

To reach these objectives we will follow 6 specific aims:

We will study the physiologic development of the nano-architecture of the CASB in animal models (Aim 1). New tools will be developed to enhance visualization and analysis of CASB 3D-data through 3D-printing and Virtual Reality (VR) imaging (Aim 2). Changes in the nano-architecture of the CASB will be analyzed in animal models of OA-pathology (Aim 3). The CASB will be studied in human samples of OA (Aim 4). Based on the data collected in Aim 1-4 we will evaluate diagnostic and treatment options (Aim 5) and will develop a new model of cartilage-CASB interaction (Aim 6).