Gillo Research Institute Discovers New Protein Regulating Cartilage and Bone Differentiation Process

Stem Cell Differentiation Varies Depending on MAST4 Presence
New Chapter Expected in Cartilage Regeneration Therapy
Research Published in 'Nature Communications'

Kim Sung-jin, CEO of MedPacto and Director of Gillo Research Institute.

[Asia Economy Reporter Lee Gwan-joo] Domestic researchers have discovered a new protein that plays a crucial role in research aimed at treating various cartilage and bone losses, such as osteoporosis and rheumatoid arthritis, chronic intractable osteoarticular diseases in the aging era.

The Gilo Research Institute, a foundation where Kim Sung-jin, CEO of MedPacto, also serves as the head of the research center, announced on the 14th that through joint research with Yonsei University, Japan's University of Tsukuba, Theragen Etex, and MedPacto, they have identified for the first time in the world that the 'MAST4' protein is a key protein determining the differentiation of mesenchymal stem cells (MSC) into cartilage or bone cells.

It is known that the differentiation of mesenchymal stem cells into cartilage and bone is intricately regulated by key transcription factors such as Sox9 and Runx2, as well as signaling pathways like TGF-beta and Wnt/beta-catenin. However, research on the key factors determining the direction of individual differentiation has been insufficient, making it difficult to apply in actual cell therapy.

The research team found that the MAST4 protein inhibits cartilage differentiation of MSCs while promoting bone differentiation. Without the MAST4 protein, MSCs differentiate into chondrocytes, and when MAST4 protein levels increase, MSCs differentiate into osteocytes.

The researchers discovered that the phosphorylation enzyme MAST4 protein, whose function was not well known, is suppressed by TGF-beta signaling during the cartilage differentiation process. MAST4 protein acts on the Sox9 protein, which plays a key role in cartilage cell differentiation and cartilage regeneration, inducing its degradation. When MAST4 is deficient, SOX9 protein is not degraded and its amount increases, significantly enhancing the gene expression of most proteins constituting cartilage. This was confirmed through cartilage differentiation cells and the endochondral ossification process in MAST4 gene-deficient mice.

This study identified the MAST4 protein, an important central mediator of the previously known TGF-beta and Wnt signaling pathways, and newly elucidated the connection in the bone-cartilage differentiation process, which is expected to contribute to the treatment of osteoarticular diseases in the future. In particular, MSCs have low immunogenicity, allowing the use of both autologous and allogeneic cells, making cell acquisition easy. After simply removing the MAST4 gene using gene editing tools, these MSCs can be transplanted, making it highly likely to become a revolutionary treatment for cartilage regeneration.

Kim Sung-jin, head of the Gilo Research Institute, explained, “The MAST4 protein is a factor that ‘determines the direction’ of mesenchymal stem cell differentiation,” adding, “By newly discovering that MAST4 protein mediates TGF-beta and Wnt signaling, we have laid the groundwork for developing effective cell therapy technologies for various osteoarticular diseases such as degenerative arthritis and osteoporosis.”

This research was published in the July issue of 'Nature Communications,' the online sister journal of the world-renowned journal 'Nature.'

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