Table 1.
Endogenous SMAs and their molecular mechanisms of action
| Name | Structural formula | Function | Cell types | Mechanism | References |
|---|---|---|---|---|---|
| Dopamine |  |
OC↓ OB↑ |
hBMSCs; human CD14+ cell-derived OC precursor cells; PDLSCs; MC3T3-E1 preosteoblasts; RAW 264.7 cells |
Activates ERK1/2, integrin α5/β1 and PI3K signaling; inhibits the cAMP/PKA/CREB pathway |
23,67,225–227 |
| Epinephrine |  |
OB↑ | ST2 cells; C2C12 cells | Activates BMP and cAMP/PKA signaling | 176 |
| Melatonin |  |
OC↓ OB↑ inflammation ↓ oxidative stress ↓ |
RAW264.7 cells; DPSCs; MC3T3-E1 cells; hBMSCs |
Activates p38/ERK signaling, the AMPK and STIM1/ ORAI1 pathways; inhibits MAPK and NFATc1 signaling |
73,228–233 |
| Adenosine |  |
OC↓ OB↑ |
BMMs (C57BL/6 mice); MSCs; MC3T3-E1 cells |
The A2B receptor inhibits the ERK1/2, p38 and NF-κB pathways (OCs); The A2B receptor and A(2A) receptor activates the Akt and Wnt pathways (OBs) |
96,97,234–236 |
| Glutamine |  |
OB↑ | HDPCs; ST2 cells; BMSCs; etc. | Activates BMP, Wnt, MAPK, and other pathways | 70,82,124 |
| Glutamic acid |  |
OB↑ | RAW264.7 cells; hFOB1.19 cells; MSCs (rat) | Activates Gln signaling | 83,237 |
| Taurine |  |
OC↓ OB↑ |
RAW264.7 cells; the MLO-Y4 cell line (an osteocyte line); the IDG-SW3 cell line (an osteocyte line); MC3T3-E1 cells; MG63 |
Activates ERK and Wnt/β-catenin signaling pathways | 74,238–240 |
| Spermidine |  |
OC↓ OB↑ inflammation ↓ oxidative stress ↓ |
chondrocytes (osteoarthritis patient); OCs (Std-ddY mice); RAW264.7 cells; human FLS cells | Inhibits the NF-κB pathway | 161,184,241,242 |
| Spermine |  |
OC↓ OB↑ |
OCs (Std-ddY mice); RAW264.7 cells; hASCs | Inhibits +NF-κB pathway; activates β-catenin | 161,243 |
| Glucosamine |  |
OB↑ | Chondrocytes (SD rats); hFOB1.19 cells | Inhibits the mTOR (OB) pathway; promotes the Wnt (chondrocyte) pathway | 117,118 |
| Acetyl choline |  |
OC↓ | Pre-OCs (murine) | (nAChRs) Inhibits c-fos and NFATc1 signaling | 244 |
| Betaine |  |
OB↑ | hOBs; hBMSCs | Activate ERK IGF‑I and Ca2+-/calmodulin-dependent kinase II signaling; Inhibit mTOR pathway | 75,245 |
| Folic acid |  |
OC↓ OB↑ |
hMSCs | N/A | 246,247 |
| Pyrroloquinoline quinone |  |
OC↓ OB↑ oxidative stress ↓ |
MSCs (female C57/BL6J mice) | Inhibit ROS and NF-κB signaling | 210,248 |
| Sphingosine-1-phosphate |  |
OB↑ | C3H10T1/2 pluripotent stem cells; SaOS-2 cells; MC3T3-E1 cells | Activate PI3K/Akt and Wnt pathways | 100,249 |
| γ-Aminobutyric acid (GABA) |  |
OB↑ | hMSCs; RAW 264.7 cells | Activate TNFAIP3 signaling | 122 |