Table 2.
Drug-SMAs and their molecular mechanisms of action
| Name | Clinical application | In vitro | In vivo | Function | Mechanism | Ref. |
|---|---|---|---|---|---|---|
| Deferoxamine | Acute iron poisoning | BMMs (C57BL/6 mice); MSCs | GIOP |
OC↓ OB↑ angiogenesis ↑ |
Inhibits the electron transport chain and MAPK pathways; activates the HIF-1 and TGF-β1/Smad2 pathways | 115,138,250,251 |
| Metformin | Type 2 diabetes mellitus | PDLSC;s hEDT-SCs; MC3T3E1 cells; MSCs; ACSs; CV-MSCs | T2DM patients; OP; OVX |
OC↓ OB↑ |
Inhibits RANKL; activates the AMPK, Wnt, Akt/Nrf2, BMP-4/Smad/Runx2 pathways | 121,206,252–257 |
| Benzydamine | Anti-inflammatory analgesics | BMMs (C57BL/6 mice) | OVX; LIOP |
OC↓ OB↑ inflammation ↓ |
Inhibits NF-κB, ERK and p38 signaling | 45 |
| Cetirizine |
Treatment of allergic conjunctivitis, etc. |
N/A | CSE | OC↓ | N/A | 46 |
| Cimetidine | Duodenal ulcer, gastric ulcer, reflux esophagitis, stress ulcer Zollinger–Ellison syndrome and chronic urticaria, etc. | BMMs (Lewis rat) | rat adjuvant arthritis |
OC↓ inflammation ↓ |
Inhibits the histamine H2-receptor | 47 |
| Meclizine | Motion sickness | BMMs (C57BL/6 mice) | OVX | OC↓ | Inhibits the NF-κB and MAPK pathways | 160 |
| Tranylcypromine | Depression | BMMs (C57BL/6 mice) | GIOP; OVX; LIOP |
OC↓ OB↑ |
Inhibits the Akt and mTOR pathways; activates the BMP pathway | 119,258 |
| Piperazine | Roundworm and pinworm | MC3T3-E1 cells | N/A | OB↑ | N/A | 58 |
| Doxycycline | Antibacterial and anti-infection agent | BM-MSCs | SIDR | OB↑ | Activates the Wnt/β-catenin pathway | 48 |
| Enoxacin | Antibacterial and antibiotic | RAW 264.7 cells; primary marrow cells | N/A | OC↓ | Inhibit ORV | 174 |
| Tofacitinib | Rheumatoid arthritis | MSCs | OVX; AM; adjuvant-induced arthritis |
OC↓ OB↑ inflammation ↓ |
Inhibits JAK and RANKL signaling; activates the Wnt pathway | 27,28,259 |
| Baricitinib | Rheumatoid arthritis | MSCs; PMCCs (male ddY mice) | OVX; AM |
OC↓ OB↑ inflammation ↓ |
Inhibits JAK and RANKL signaling; activates Wnt pathway | 27,45 |
| Benidipine | Essential hypertension | BMSCs | OVX | OB↑ | Activates the Wnt/β-catenin pathway | 86 |
| Glimepiride | Type 2 diabetes mellitus | OB (Sprague–Dawley rats) | N/A | OB↑ | Activates the PI3K/Akt/eNOS pathway | 31 |
| Bortezomib | Adult patients with multiple myeloma | BMMs (female ICR mice); osteoblast-derived UMR106-01 cells; POBs |
OVX; FRIO; AIA |
OC↓ OB↑ inflammation ↓ |
Inhibits the proteasome and NF-κB pathway | 29,40,260 |
| Odanacatib |
Osteoporosis (Phase III) |
N/A | OVX monkeys; ROFR |
OC↓ OB↑ inflammation ↓ |
Inhibits Cathepsin K | 261–263 |
| Saracatinib | Cancer, osteosarcoma, etc. (Phase II) | RAW 264.7 cells; PC-3 prostate cancer cells; rabbit OCs; fetal calvarial mouse OCs; hPBMCs | OLIP | OC↓ | Inhibits the Src, NF-κB and p38 pathway | 41,42 |
| Dasatinib | Lymphoblastic or chronic myeloid leukemia | hBM-MSCs; hMSCs; MG-63; PBMCs | OIRA; CRMO |
OC↓ OB↑ inflammation ↓ |
Inhibits Src, ERK1/2 pathway; activates the Wnt/β-catenin and Hippo-YAP pathways | 129,130,193 |