Table 2. New OA drugs and emerging therapeutics investigated in clinical studies (*) or preclinical animal studies.
| Mode of action | Targets | Potential therapeutics |
|---|---|---|
| Chondrogenic differentiation | BMP-7* FGF* PRP (containing several kinds of growth factors)* | rhBMP-7 (OP-1)70 rhFGF-18 (sprifermin)76 Autologous PRP78–80 |
| Inhibition of hypertrophy and ossification | PTH/PTHrP receptor Hedgehog signaling | rhPTH (1–34) (teriparatide, Forteo),126 rhPTHrP (1–40)123 Smo inhibitor (HhAntag, LDE223)127,128 |
| Inhibition of matrix degradation | MMP13 Adamts-5 Syndecan-4 | MMP13 inhibitor (CL82198)118 Adamts-5 inhibitor (114810)119 Syndecan-4-specific antibody120 |
| Inhibition of inflammation | IL-1β* HSA* Methotrexate* | IL-1β receptor antagonist,71 IL-1β receptor antibody (AMG108)72 a <5-kDa ultrafiltrate of HSA (Ampion)83,84 Methotrexate85–88 |
| Reduction in pain | β-NGF* | Monoclonal antibody against β-NGF (Tanezumab)73–75 |
| Subchondral bone | TGF-β Wnt/b-catenin | TGF-β type I receptor inhibitor (SB-505124), TGF-β antibody (1D11)129 Wnt antagonist (Dkk-1)131 |
β-NGF, β-nerve growth factor; BMP-7, bone morphogenetic protein-7; OP-1, osteogenic protein-1; Dkk-1, dickkopf-related protein-1; FGF, fibroblast growth factor; HSA, human serum albumin; PTH, parathyroid hormone; PTHrP, parathyroid hormone-related protein; rhBMP-7, recombinant human BMP-7; rhFGF; recombinant human FGF; rhPTHrP; recombinant human PTHrP; MMP13, matrix metalloproteinase 13; OA, osteoarthritis; PRP, platelet-rich plasma; TGF-β, transforming growth factor-β.