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Table 1 Emerging intra-articular therapies for osteoarthritis

From: Stem cells and other innovative intra-articular therapies for osteoarthritis: what does the future hold?

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
Botulinum toxin [2932] 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
Fibroblast growth factor-18 (FGF-18) [41, 42, 46] 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
Insulin-like growth factor (IGF) [42, 43, 47] Improvement in cartilage homeostasis by balancing proteoglycan synthesis and breakdown; reduction in synovial inflammation
Caspase inhibitors [48, 49] 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