Therapy/Drug development stage | Proposed mechanism of action |
---|---|
Evidence from Human Studies | |
Interleukin-1 (IL-1) inhibitor [25, 26, 44] 2 Phase II/III trials | Inhibition of IL-1, a pro-inflammatory cytokine that promotes cartilage degradation |
Human autologous conditioned serum [27, 28] 2 Phase II/III trials | Production of anti-inflammatory cytokines such as IL-1 receptor antagonist, IL-4, IL-10, and IL-13 |
3 Phase II/III trials | Inhibition of release of release of Substance P, calcitonin gene-related protein and glutamate from primary afferent neuron terminals |
Recombinant human bone morphogenetic protein-7 (BMP-7) [38, 45] 1 Phase I trial | Stimulation of proteoglycan, collagen and hyaluronic acid synthesis; induction of receptors, prevention of catabolism of cartilage components by interleukin (IL)-1 |
Human platelet rich plasma (PRP) [39, 40] Case series (n = 14) | Stimulation of chondrogenesis, increase in hyaluronic acid production, stabilization of angiogenesis |
Evidence from Animal Models | |
Stimulation or stabilization of bio-synthesis of cartilage matrix components | |
Platelet-derived growth factor (PDGF) [43] | Increase in cell proliferation and proteoglycan production; stimulation of meniscal cell proliferation and migration |
Improvement in cartilage homeostasis by balancing proteoglycan synthesis and breakdown; reduction in synovial inflammation | |
Inhibition of chondrocyte death apoptosis | |
Human Kallistatin [50] | Suppression of inflammatory responses and reduce cell apoptosis |
Interleukin-6 (IL-6) inhibitor [51] | Inhibition of hypoxia-inducible factor 2 alpha-induced cartilage destruction by regulating matrix metalloproteinase 3 (MMP3) and MMP13 |
Recombinant human PRG4 (rhPRG4) [52] | Replacement of lubricin, that has lubricant and anti-adhesive properties and is chondroprotective |
Recombinant human OPG (rHuOPG) [53] | Suppression of chondrocyte apoptosis |
Leptin [54] | Stimulation of synthesis of IGF-1 and TGF beta1 to stimulate chondrocytes to repair extracellular matrix |
Mu-opioid receptor [55] | Reduction of substance P and neurotransmitter release from sensory nerve endings peripherally and centrally |
Dehydroepiandrosterone [56] | Modulate the imbalance between matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases 1 (TIMP-1) |
Berberine, a traditional Chinese medication [57] | Reduction of MMP-3 and MMP-13 levels |
Evidence from in vitro studies | |
Fibroblast growth factor-2 (FGF-2) [58] | Stimulation of chondrocyte progenitor cells |
N-acetylcysteine [59] | Increase in chondrocyte viability by reducing oxidative damage |