Sdc4, also known as Syndecan 4, is a cell surface heparan sulfate proteoglycan. It is involved in regulating multiple cellular functions such as cytoskeleton organization, cell adhesion, and cell migration. Sdc4 participates in various signaling pathways including the MAPK signaling pathway, and is also associated with the PI3K/AKT pathway [2,3]. It plays a significant role in human tumorigenesis and development, and is of great biological importance in maintaining matrix homeostasis in tissues [2,4,1].

Sdc4 knockout (KO) mouse models have provided valuable insights. In Sdc4 KO mice, there was a severe reduction in vertebral trabecular and cortical bone mass, along with altered biomechanical properties of vertebrae due to elevated osteoclastic activity. The intervertebral disc also showed subtle phenotypic changes, with reduced mature collagen crosslinks and increased chondroitin sulfate levels in certain compartments [1]. In pancreatic cancer cells, knocking out SDC4 markedly impaired macropinocytosis, colony formation, as well as xenograft tumor initiation and growth [2].

In conclusion, Sdc4 is crucial for maintaining vertebral bone and extracellular matrix homeostasis in the intervertebral disc. It also plays a role in tumor-related processes such as macropinocytosis and tumor growth. The study of Sdc4 using KO mouse models has enhanced our understanding of its functions in these biological processes and disease conditions, providing potential targets for treating related diseases like osteoporosis and cancer [1,2].