Ccn2, also known as connective tissue growth factor (CTGF), is a matricellular protein. It is involved in regulating various biological activities such as cell growth, invasion, and migration, and is associated with pathways like TGF-β, ILK-Syk, and α6β1 integrin receptor-related signaling. Ccn2 is crucial for the harmonized development of tissues like cartilage and bone in the skeletal system [1,3].

A monoallelic variant in CCN2 causes autosomal dominant spondyloepimetaphyseal dysplasia with low bone mass. Osteoblast lineage-specific Ccn2-deficient mice (Ccn2fl/fl;Prx1Cre) recapitulated phenotypes including low bone mass, decreased bone formation, increased bone resorption, and abnormal growth plate formation, highlighting the critical role of CCN2 in osteogenesis [2].

In conclusion, Ccn2 plays essential roles in tissue development, especially in the skeletal system. The Ccn2-deficient mouse model has revealed its significance in osteogenesis and bone-related diseases, providing insights into the understanding of skeletal dysplasia mechanisms and potential therapeutic targets.

References:

1. Ghosh, Priya, Dey, Ankita, Nandi, Suvendu, Das, Subhayan, Mandal, Mahitosh. 2025. CTGF (CCN2): a multifaceted mediator in breast cancer progression and therapeutic targeting. In Cancer metastasis reviews, 44, 32. doi:10.1007/s10555-025-10248-4. https://pubmed.ncbi.nlm.nih.gov/39945880/

2. Li, Shanshan, Shao, Rui, Li, Shufa, Zou, Weiguo, Zhang, Zhenlin. 2024. A monoallelic variant in CCN2 causes an autosomal dominant spondyloepimetaphyseal dysplasia with low bone mass. In Bone research, 12, 60. doi:10.1038/s41413-024-00364-2. https://pubmed.ncbi.nlm.nih.gov/39414788/

3. Kubota, Satoshi, Takigawa, Masaharu. . Cellular and molecular actions of CCN2/CTGF and its role under physiological and pathological conditions. In Clinical science (London, England : 1979), 128, 181-96. doi:10.1042/CS20140264. https://pubmed.ncbi.nlm.nih.gov/25294165/