Osteopontin (OPN)/SPP1: from its biochemistry to biological functions in the innate immune system and the central nervous system (CNS)

Abstract

Osteopontin (OPN) is a multifunctional protein, initially identified in osteosarcoma cells with its role of mediating osteoblast adhesion. Later studies revealed that OPN is associated with many inflammatory conditions caused by infections, allergic responses, autoimmunity and tissue damage. Many cell types in the peripheral immune system express OPN with various functions, which could be beneficial or detrimental. Also, more recent studies demonstrated that OPN is highly expressed in the central nervous system (CNS), particularly in microglia during CNS diseases and development. However, understanding of mechanisms underlying OPN's functions in the CNS is still limited. In this review, we focus on peripheral myeloid cells and CNS-resident cells to discuss the expression and functions of OPN.

Keywords: SPP1; innate immunity; intracellular osteopontin (iOPN); myeloid cells; secreted osteopontin (sOPN).

Graphical Abstract

Fig. 1.

OPN expression and its outcomes in various cell types. OPN receptors, integrins and CD44, are commonly expressed on the surface of cell types described here. sOPN has been extensively studied, particularly in peripheral immunity, and generally promotes cell migration and effector functions, such as opsonization and cell proliferation. iOPN has been studied in the immune system but not in the CNS-resident cells. For some cells, mainly CNS-resident cells other than microglia, OPN expression was reported but not to the extent of sOPN and/or iOPN. For astrocytes and neurons, we interpreted that sOPN and/or iOPN may be produced based on data from published articles (indicated as ‘sOPN?’ or ‘iOPN?’). Oligodendrocytes and OPC detect sOPN, but the source of sOPN is unclear in vivo. Degenerated neurons are considered to be opsonized by sOPN for phagocytosis by microglia.