Ucma-KO Mouse

Ucma, also known as Upper zone of growth plate and Cartilage Matrix Associated protein or Gla Rich Protein (GRP), is a highly conserved tyrosine-sulphated secreted protein. It is a member of the vitamin K-dependent protein family. Ucma seems to play crucial roles in processes related to mineralization, chondrogenic and osteogenic differentiation, and may be involved in skeletal homeostasis [3,4]. It is associated with the BMP-2-SMAD1/5/8 osteo/chondrogenic signalling pathway [1].

In Ucma-deficient mouse models, despite previous in vitro implications in calcification and ossification, normal skeletal and cartilage development was not affected [2]. However, VSMCs from Ucma/GRP-/-mice showed increased mineralisation and up-regulation of osteo/chondrogenic markers, along with decreased expression of the mineralisation inhibitor MGP, indicating that Ucma/GRP is an inhibitor of mineralisation. Ucma/GRP also inhibits the BMP-2-SMAD1/5/8 osteo/chondrogenic signalling pathway in VSMCs treated with elevated phosphate concentrations [1].

In conclusion, model-based research, especially using Ucma-deficient mouse models, has revealed that Ucma plays a significant role in regulating osteo/chondrogenic differentiation and phosphate-induced mineralisation of VSMCs. Although not necessary for normal skeletal development in mice, it may be involved in skeletal homeostasis and could be relevant in disease conditions related to vascular and soft-tissue calcification, such as in chronic kidney disease patients where vascular calcification is prevalent [1,2].

References:

1. Willems, Brecht A, Furmanik, Malgorzata, Caron, Marjolein M J, Reutelingsperger, Chris P M, Schurgers, Leon J. 2018. Ucma/GRP inhibits phosphate-induced vascular smooth muscle cell calcification via SMAD-dependent BMP signalling. In Scientific reports, 8, 4961. doi:10.1038/s41598-018-23353-y. https://pubmed.ncbi.nlm.nih.gov/29563538/

2. Eitzinger, Nicole, Surmann-Schmitt, Cordula, Bösl, Michael, von der Mark, Klaus, Stock, Michael. 2011. Ucma is not necessary for normal development of the mouse skeleton. In Bone, 50, 670-80. doi:10.1016/j.bone.2011.11.017. https://pubmed.ncbi.nlm.nih.gov/22155508/

3. Bordoloi, Jijnasa, Dihingia, Anjum, Kalita, Jatin, Manna, Prasenjit. 2018. Implication of a novel vitamin K dependent protein, GRP/Ucma in the pathophysiological conditions associated with vascular and soft tissue calcification, osteoarthritis, inflammation, and carcinoma. In International journal of biological macromolecules, 113, 309-316. doi:10.1016/j.ijbiomac.2018.02.150. https://pubmed.ncbi.nlm.nih.gov/29499263/

4. Surmann-Schmitt, Cordula, Dietz, Uwe, Kireva, Trayana, von der Mark, Klaus, Stock, Michael. 2007. Ucma, a novel secreted cartilage-specific protein with implications in osteogenesis. In The Journal of biological chemistry, 283, 7082-93. doi:. https://pubmed.ncbi.nlm.nih.gov/18156182/