Synergistic effect of IGF-1 and OP-1 on matrix formation by normal and OA chondrocytes cultured in alginate beads

Chubinskaya, Susan; Hakimiyan, Arnavaz; Pacione, Carol; Yanke, Adam B.; Rappoport, L.; Aigner, Thomas; Rueger, David C.; Loeser, Richard F.

doi:10.1016/j.joca.2006.10.004

Cited by 83 publications

(80 citation statements)

References 47 publications

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“…Despite the diminished ability of IGF-I to decrease catabolism in aged and OA cartilage, studies suggest that a combination of IGF-I and BMP-7 results in greater repair potential than either growth factor alone [15,54]. These studies demonstrated that in general, BMP-7 was more potent than IGF-I in stimulating matrix synthesis in aged and OA cells, but the greatest increase in matrix synthesis was observed after combination treatment with BMP-7 and IGF-I.…”

Section: Insulin-like Growth Factor-imentioning

confidence: 99%

The Role of Growth Factors in Cartilage Repair

Fortier

Barker

Strauss

et al. 2011

Clinical Orthopaedics &Amp; Related Research

552

449

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Section: Insulin-like Growth Factor-imentioning

confidence: 99%

The Role of Growth Factors in Cartilage Repair

Fortier

Barker

Strauss

et al. 2011

Clinical Orthopaedics &Amp; Related Research

552

449

View full text Add to dashboard Cite

show abstract

“…Interleukin-1 receptor antagonist protein (IL-1Ra) can inhibit cartilage matrix degeneration by blocking the adverse effects of interleukin-1 (IL-1) in OA (Frisbie et al, 2002). Insulin-like growth factor-1 (IGF-1) promotes the synthesis of cartilage matrix (Chubinskaya et al, 2007). These results show that bFGF, IL-1Ra and IGF-1 are potential candidate cytokines in gene therapy of OA.…”

Section: Introductionmentioning

confidence: 99%

Effects of adenovirus-mediated bFGF, IL-1Ra and IGF-1 gene transfer on human osteoarthritic chondrocytes and osteoarthritis in rabbits

et al. 2010

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Abbreviations: ACLT, anterior cruciate ligament transaction; ADAMTS, a disintegrin and metalloproteinase with thrombospondin motifs; bFGF, basic fibroblast growth factor; Ct, threshold cycle; DMMB, dimethylmethylene blue; ECM, extracellular matrix; GAG, glycosaminoglycan; IGF-1, insulin-like growth factor-1; IL-1Ra, interleukin-1 receptor antagonist protein; MMP, matrix metalloproteinase; OA, osteoarthritis; TIMP, tissue inhibitor of metalloproteinase AbstractThe study investigated the effects of adenovirus-mediated gene transfection of basic fibroblast growth factor (bFGF), bFGF combined with interleukin-1 receptor antagonist protein (IL-Ra) and/or insulin-like growth factor-1 (IGF-1) both in human osteoarthritis (OA) chondrocytes and rabbits OA model. Human OA chondrocytes were delivered by adenovirus-mediated bFGF, IL-Ra and IGF-1 vectors, respectively. Chondrocyte proliferation, glycosaminoglycan (GAG) content, expression of type II collagen, ADAMTS-5, MMP-13, MMP-3 and TIMP-1 were determined. Rabbit OA model was induced by anterior cruciate ligament transaction (ACLT) in knees. Adenoviral vectors encoding human bFGF, IL-Ra and IGF-1 were injected intraarticularly into the knee joints after ACLT. The effects of adenovirus-mediated gene transfection on rabbit OA were evaluated. In vitro, the transfected genes were expressed in cell supernatant of human OA chondrocytes. AdbFGF group significantly promoted chondrocyte proliferation, and increased GAG and type II collagen synthesis than in the OA group. As two or three genes were transfected in different combinations, there was significant enhancement on the GAG content, type II collagen synthesis, and TIMP-1 levels, while ADAMTS-5, MMP-13, and MMP-3 levels were reduced. In vivo, the transfected genes were expressed in synovial fluid of rabbits. Intraarticular delivery of bFGF enhanced the expression of type II collagen in cartilage and decreased cartilage Mankin score compared with the OA control group (P = 0.047; P ＜ 0.01, respectively). Multiple-gene transfection in different combinations showed better results than bFGF transfection alone. This study suggests that bFGF gene transfection is effective in treating experimental OA. Multiple gene transfection has better biologic effects on OA.

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“…4) For example, BMP-7, a member of transforming growth factor-β (TGF-β)/BMP superfamily, is a representative anabolic growth factor to repair the articular cartilage through the stimulation of cartilage-specific extracellular proteins such as collagen type II, aggrecan, decorin, fibronectin and hyaluronan. [23][24][25] Recently, Hunter et al, performed the phase 1 safety and tolerability study of BMP-7 in symptomatic knee OA and reported that patients received the BMP-7 were a trend toward symptomatic improvement without toxicity.…”

Section: Discussionmentioning

confidence: 99%

Biological Effects of the Herbal Plant-Derived Phytoestrogen Bavachin in Primary Rat Chondrocytes

Lee

Cho

Kang

et al. 2015

Biological & Pharmaceutical Bulletin

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The aim of this study was to examine the anabolic and anticatabolic functions of bavachin in primary rat chondrocytes. With bavachin treatment, chondrocytes survived for 21 d without cell proliferation, and the proteoglycan content and extracellular matrix increased. Short-term monolayer culture of chondrocytes showed that gene induction of both aggrecan and collagen type II, major extracellular matrix components, was significantly upregulated by bavachin. The expression and activities of cartilage-degrading enzymes such as matrix metalloproteinases and a disintegrin and metalloproteinase with thrombospondin motifs were inhibited significantly by bavachin, while tissue inhibitors of metalloprotease were significantly upregulated. Bavachin inhibits the expression of inducible nitric oxide synthase, a representative catabolic factor, and downregulated the expression of nitric oxide, cyclooxygenase-2, and prostaglandin E 2 in a dose-dependent manner in chondrocytes. Our results suggest that the bavachin has anabolic and potent anticatabolic biological effects on chondrocytes, which may have considerable promise in treating articular cartilage degeneration in the future.Key words Osteoarthritis (OA); articular cartilage; chondrocyte; phytoestrogen; bavachin Osteoarthritis (OA) is a representative degenerative disease associated with aging and is the most common type of arthritis.1) The clinical symptoms of OA are defined as chronic joint pain, stiffness, and loss of mechanical joint function caused by progressive cartilage degeneration.2) Moreover, the prevalence of OA is largely age-dependent and is increased significantly in people over age 65.1) Although the prevalence of OA is less in those under 40, prevalence is increasing in these populations because of obesity, individual heredity, mechanical injuries, and surgical trauma of joints.1) The socioeconomic burden associated with OA is increased by both direct medical expenses and indirect costs caused by decreased productivity in the workplace.2) Although various studies on the pathophysiological etiologies of OA are ongoing, many of the factors causing this disease are still unknown. Hence, clinical treatments of OA have been mainly focused on relieving chronic joint pain by suppressing inflammation in the degenerative joint more so than on cartilage regeneration.Homeostasis of articular cartilage is precisely regulated by the balance between synthesis (anabolism) and degradation (catabolism) of the extracellular matrix (ECM), which is mainly composed of collagen Type II and proteoglycan synthesized from chondrocytes to maintain mechanical function in response to a compressive overload on joints.3) However, perturbations in chondrocytes with normal metabolic properties induce the progressive destruction of ECM through the up-regulation of cartilage-degrading enzymes such as matrix metalloproteinase (MMP)-13, MMP-3, MMP-1, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 and ADAMTS-5.3) Recent research has focused on cartilage regenerati...

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Synergistic effect of IGF-1 and OP-1 on matrix formation by normal and OA chondrocytes cultured in alginate beads

Abstract: The results obtained in the current study suggest that combined therapy with IGF-1 and OP-1 may have a greater potential in treating cartilage defects seen in OA than use of either growth factor alone.

Cited by 83 publications

References 47 publications

The Role of Growth Factors in Cartilage Repair

The Role of Growth Factors in Cartilage Repair

Effects of adenovirus-mediated bFGF, IL-1Ra and IGF-1 gene transfer on human osteoarthritic chondrocytes and osteoarthritis in rabbits

Biological Effects of the Herbal Plant-Derived Phytoestrogen Bavachin in Primary Rat Chondrocytes

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