The crucial role of SPP1 in osteoporosis, osteoarthritis, and cancer

Abstract

Osteopontin (OPN), also known as secreted phosphoprotein 1(SPP1), is a highly glycosylated and phosphorylated acidic protein, which is a multifunctional glycoprotein expressed in numerous cell types. SPP1 is involved in the attachment of osteoclasts to mineralized bone matrix, inflammatory reaction, cell recruitment, and tissue repair, and plays an important role in bone formation, fibrosis, immune diseases, and cancer. The role of SPP1 in osteoporosis, osteoarthritis and cancer is multi-faceted. While it holds potential therapeutic value, it also presents certain limitations. This review integrates the molecular structural characteristics of SPP1, including isoform variants and post-translational modifications, with its pathophysiological functions. It highlights the regulatory roles of SPP1 in these diseases: maintaining the dynamic balance between bone resorption and formation in osteoporosis, promoting cartilage degeneration and inflammation in osteoarthritis, and driving tumor progression in cancer through the activation of pathways such as PI3K/AKT/mTOR. Furthermore, SPP1 regulates tumor-associated macrophages and fibroblasts within the tumor microenvironment, thereby facilitating immune evasion and metastasis. The article also underscores the potential value of precisely modulating SPP1 activity in the treatment of osteoporosis and osteoarthritis and suggests a combined therapeutic strategy targeting SPP1, offering novel insights into overcoming the limitations of single-target cancer therapies.