Table 1.

Arguments implying a role for alterations in TGFβ signaling in osteoarthritis development

Genetic studies point to a role for TGFβ in osteoarthritis

Mice that express a dominant negative TGFβ type II receptor in skeletal tissues showed enhanced chondrocyte hypertrophy and osteoarthritis

Mice deficient for Smad3 or latent TGFβ binding protein 3 demonstrated enhanced chondrocyte hypertrophy and osteoarthritis

Cartilage protective effects of TGFβ are lost in ageing mice

ALK1/ALK5 expression ratio is increased in cartilage in ageing mice and experimental osteoarthritis

ALK1 overexpression results in MMP-13 upregulation in chondrocytes

Blocking ALK5 expression, using siRNA, leads to elevated expression of MMP-13

In human osteoarthritis cartilage, ALK1 expression and MMP-13 expression significantly correlate

Smad2/3 signaling inhibits, while Smad1/5/8 signaling stimulates, progression of chondrocyte differentiation

In osteoarthritis, synthesis of matrix molecules (type II collagen) is increased - indicating no dominant role for catabolic cytokines

Alterations in TGFβ signaling in osteoarthritis can provide an explanation for the enigmatic observation of concomitant increased synthesis of matrix molecules (type II collagen) and increased MMP-13 production

MMP-13, matrix metalloproteinase 13; TGFβ, transforming growth factor beta.