The role of the cartilage protein Ucma in degenerative and inflammatory arthritis

• Applicant: Privatdozent Dr. Michael Stock
• Subject Area: Rheumatology
• Term: from 2014 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 257095132

Ucma is a recently identified secreted cartilage protein. It is virtually exclusively expressed in cartilage, and knockdown of Ucma in zebrafish by morpholino RNA results in a severely disturbed skeletal development. In contrast, however, Ucma-deficient mice develop normally. Therefore, the biological role of Ucma in mammals is largely unknown to date, although we had previously shown that Ucma inhibits the osteogenic differentiation of murine and human progenitor cells in vitro. Using Ucma-deficient mice, we show here that Ucma has a protective effect on cartilage integrity during experimental osteoarthritis. Moreover, we demonstrate that during experimental osteoarthritis Ucma-deficient mice do not exhibit the sclerotic bone phenotype, characterised by an increase in osteoblast and osteoclast numbers, as observed in wild-type mice. This indicates a potential role of Ucma in the communication between cartilage and bone during osteoarthritis.During the proposed project we will investigate the protective mechanisms of Ucma on cartilage integrity during experimental osteoarthritis. Moreover, we will study, by which means Ucma affects bone remodelling in experimental osteoarthritis and thereby contributes to cartilage-bone communication. We will also assess a potential effect of Ucma on cartilage damage and bone turnover in experimental inflammatory arthritis. In order to evaluate a conceivable therapeutic potential of Ucma in the treatment of degenerative and/or inflammatory joint diseases, we will establish a gain-of-function mouse model for Ucma, and investigate the progression of experimental osteoarthritis and inflammatory arthritis in the presence or absence of excess levels of Ucma. Finally, we will investigate, whether the role of Ucma in murine joint diseases can be translated to the human system.

• DFG Programme: Research Grants
• Participating Persons: Professor Dr. Klaus Engelke; Professor Dr. Kolja Gelse