Dr. Chenghai Zhang – The Role of Creb5, a master transcription factor, in aging and osteoarthritis

Dr. Chenghai Zhang completed his PhD in Biology at Nanjing University, China. During this time, he made significant contributions regarding the regulation of airway smooth muscle pathophysiology. He currently is an instructor in Biological Chemistry and Molecular Pharmacology, Harvard Medical School. Here his research is focused cartilage, bone and joint development and related disorders. Worldwide, musculoskeletal conditions are the leading contributing factor to disability. Knowing this Dr. Zhang became particularly interested in how the different cell fates are determined during development in the musculoskeletal system, and how the maintenance of the cell fates is dysfunctionally regulated in musculoskeletal conditions.

Cartilage helps absorb the shock of movement and allows bones to glide over each other. Articular cartilage is the smooth white tissue that covers the ends of bones where they come together to form joints. Chondrocytes are cells in cartilage which produce collagen, and proteoglycans such as aggrecan and lubricin, all of which are necessary in the maintenance of health articular cartilage. Lubricin is of particular interest as this proteoglycan is secreted by the most superficial layer of the articular cartilage and is known to be essential for proper joint lubrication and maintenance of both the articular cartilage itself and synovial tissue (the thin, loose vascular connective tissue that makes up the membranes surrounding joints and the sheaths protecting tendons where they pass over bony prominences).

In osteoarthritis and aging, articular cartilage begins to break down and bones end up rubbing against each other, causing inflammation, pain, and joint stiffness. Osteoarthritis, which affects more than 30 million American adults over the age of 25, is the most common form of arthritis. A hallmark of both aging joints and osteoarthritic joints is the loss of superficial zone cells in articular cartilage, which are marked by lubricin expression.

Dr. Zhang previously identified a master transcription factor, Creb5, that regulates the formation of the synovial joints, specify the articular chondrogenic lineage, and initiates/maintains the expression of lubricin expression in articular chondrocytes. As an ANRF scholar Dr. Zhang plans to build on this foundation by studying the mechanism of how Creb5 regulates synovial joints formation during the embryonic stage;  the role of Creb5 in regulating the formation, growth and degradation of articular cartilage during aging and in osteoarthritis conditions; and finally to test whether exogenous expression of Creb5 can protect articular cartilage degradation during the progression of aging/osteoarthritis or restore articular cartilage in surgery induced osteoarthritis.


“The long-term goal of my research is to understand the developmental mechanism of synovial joint/cartilage formation and to provide the basis to develop novel therapies to slow down or prevent the progression of human osteoarthritis.”


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