Proteoglycan 4 expression protects against the development of osteoarthritis

rAAV-mediated overexpression of TGF-β via vector delivery in polymeric micelles stimulates the biological and reparative activities of human articular chondrocytes in vitro and in a human osteochondral defect model

“…Study is also ongoing to examine the potency of the approach in relevant animal models of OA in vivo. [7][8][9][10][11][12][13][14]20 In conclusion, combining Figure S1 characterization of raaV-hTgF-β-mediated gene transfer in human osteochondral defect cultures via polymeric micelles. Notes: Defects were prepared, incubated with cy3-raaV/polymeric micelles and processed after 2 days to monitor the diffusion and bioactivity of the vectors by analysis of live fluorescence and immunohistochemical detection, respectively (magnification ×2) in cross-sections from the defects as described in the "cy3 labeling" and "histological and immunocyto/histochemical analyses" sections.…”

“…[7][8][9][10][11][12][13][14] In parallel, activation of anabolic/proliferative processes in OA has also been attempted using therapeutic genes such as the insulin-like growth factor I, 15,16 basic fibroblast growth factor-2, 17 bone morphogenetic proteins, 18 the transcription factor SOX9, 19 and proteoglycan 4. 20 The transforming growth factor-beta (TGF-β) is another highly potent agent capable of promoting cartilage repair, enhancing the proliferation of chondrocytes and production of extracellular cartilage matrix (ECM) components and preventing cartilage degradation. [21][22][23] While gene transfer and overexpression of TGF-β was evaluated in articular chondrocytes in vitro and in situ via nonviral 24,25 and classical viral (adenoviruses and retroviruses) vectors, [26][27][28] the use of such vehicles in vivo may be impaired by their low and short-term efficiencies, especially in nondividing cells like chondrocytes, by the possibility of insertional mutagenesis (retroviral vectors), and their relatively high immunogenicity (adenoviral vectors).…”

Mechanical motion promotes expression of Prg4 in articular cartilage via multiple CREB-dependent, fluid flow shear stress-induced signaling pathways

“…Because Prg4 GFPCreERt2/+ ; Rosa26 floxlacZ/+ mice were housed in either the absence or presence of a running wheel for 1 mo, after which their knees were isolated, fixed, sectioned, and immunostained to assay cellular localization of either phospho-S133 CREB (D) or CRTC1 (E). expression in the articular cartilage both has been noted to be sensitive to mechanical loading (Nugent et al 2006a,b;Jones et al 2009) and was recently found to protect against the development of osteoarthritis (Ruan et al 2013), we wondered whether voluntary wheel running might induce the expression of Prg4 in articular cartilage and thereby slow the progression of osteoarthritis. By employing Prg4…”

“…Col2-driven overexpression of lubricin in the articular cartilage has recently been shown to protect this tissue from degradation following surgically induced joint destabilization (Ruan et al 2013), suggesting that lubricin may somehow counter the signaling pathways that lead to cartilage destruction. Hence, an understanding of the signals that regulate lubricin expression in the articular cartilage could potentially provide a therapeutic opportunity to modulate expression of this gene and thus stem the degradation of articular cartilage observed during osteoarthritis.…”

Hydrogels and bioreactors for cartilage research and functional tissue engineering

“…PRG4 and several other splicing variants such as lubricin, megakaryocyte stimulating factor, and superficial zone protein are encoded by the gene PRG4 [28]. The over-expression of this gene in cartilage protects against the development of degenerative joint conditions, further emphasizing its importance for the maintenance of cartilage homeostasis [32].…”