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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 [29–32]

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