Fig. 2.

Literature analysis, classification, and mechanisms of SMA action. a Classification of amines. Amines are classified as primary, secondary, or tertiary ammonium compounds. Pyrrolidine and piperidine are secondary amines, and pyridine is a tertiary amine. b Classification of SMAs with osteotropic activity. Eighty-two kinds of SMAs associated with bone homeostasis include 16 endogenous and 66 exogenous SMAs. Exogenous SMAs are classified into three categories: alkaloid-SMAs, drug-SMAs (used as drugs in clinical applications), and other-SMAs. Data were obtained from the Web of Science using keywords (osteo- or bone) (amine/small molecular/alkaloid/drug) (until Jan 2022). c An analysis of the publications. Data were obtained from the Web of Science using keywords (osteo- or bone) and each name of the aforementioned 82 SMAs. d Possible approaches by which SMAs affect cells directly or indirectly. In a direct approach, SMAs bind to receptors on the cell surface or nuclear receptors inside cells or the mitochondrial membrane after entering cells through active or passive transport. In an indirect approach, cell behaviors are regulated by SMAs binding to extracellular matrix receptors, which further affects membrane proteins on the cell surface or influences the extracellular microenvironment, such as the pH value