Cytokines and Growth Factors in the Treatment of Osteoarthritis: What Could be the Best Disease Modifying Drugs

Martel‐Pelletier, Johanne; Tardif, Ginette; Laufer, Stefan; Pelletier, J.-P.

doi:10.2174/1568014054065285

Cited by 5 publications

(5 citation statements)

References 154 publications

(185 reference statements)

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“…The functional limitation in the affected joint, which is caused by progressive degradation of cartilage and subchondral tissue remodeling, leads to bone deformity [ 1 ]. It is reported that metabolic interactions between cartilage and bones play pivotal roles in the pathogenesis of OA [ 2 ]. During OA progression, activated osteoblasts induce the production of matrix metalloproteinases (MMPs) by chondrocytes, which leads to cartilage degradation [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Suppressive Effect of the n‐Hexane Extract of Litsea japonica Fruit Flesh on Monosodium‐Iodoacetate‐Induced Osteoarthritis in Rats

Kim

Choi

Yang

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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We examined the antiosteoarthritic effect of the n-hexane extract of Litsea japonica fruit flesh (LJF-HE) in a rat model of monosodium-iodoacetate- (MIA-) induced osteoarthritis. LJF-HE significantly reduced the difference in weight-bearing capabilities of the hind paws between healthy and MIA-treated rats. Histological examination of the knee joints indicated that LJF-HE suppressed cartilage and bone destruction. Additionally, there were decreases in the expression of matrix metalloproteinase-2 and metalloproteinase-9 and cyclooxygenase-2 in the joints. The serum levels of deoxypyridinoline (DPD) and osteocalcin, which are markers of bone metabolism, also decreased. Furthermore, LJF-HE significantly suppressed infiltration of inflammatory cells into the synovium and inhibited the expression of proinflammatory cytokines such as tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1, and IL-6 in the joints and serum. The serum levels of leukotriene B4 and lipoxygenase were also significantly lowered by LJF-HE. Finally, LJF-HE inhibited the production of nitric oxide, prostaglandin E2, IL-6, and TNF-α in lipopolysaccharide-activated macrophages, which might be associated with inhibited phosphorylation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase. Our data suggest that LJF-HE has an anti-inflammatory effect and may have potential as an antiosteoarthritic agent.

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Section: Introductionmentioning

confidence: 99%

Suppressive Effect of the n‐Hexane Extract of Litsea japonica Fruit Flesh on Monosodium‐Iodoacetate‐Induced Osteoarthritis in Rats

Kim

Choi

Yang

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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“…The approach for treatment of OA is often multifaceted and relies upon disease‐modifying OA agents (Dieppe and Lohmander, 2005; Martel‐Pelletier et al., 2005). The major objective of treatment is to minimise joint pain by reducing the inflammation, as well as to slow the progression of the osteopathy.…”

Section: Introductionmentioning

confidence: 99%

Comparative therapeutic efficacy and safety of type‐II collagen (uc‐II), glucosamine and chondroitin in arthritic dogs: pain evaluation by ground force plate

Gupta

Canerdy

Lindley

et al. 2011

Animal Physiology Nutrition

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The investigation was conducted on client-owned moderately arthritic dogs with two objectives: (i) to evaluate therapeutic efficacy of type-II collagen (UC-II) alone or in combination with glucosamine hydrochloride (GLU) and chondroitin sulphate (CHO), and (ii) to determine their tolerability and safety. Dogs in four groups (n = 7-10), were treated daily for a period of 150 days with placebo (Group-I), 10 mg active UC-II (Group-II), 2000 mg GLU + 1600 mg CHO (Group-III), and UC-II + GLU + CHO (Group-IV). On a monthly basis, dogs were evaluated for observational pain (overall pain, pain upon limb manipulation, and pain after physical exertion) using different numeric scales. Pain level was also measured objectively using piezoelectric sensor-based GFP for peak vertical force and impulse area. Dogs were also examined every month for physical, hepatic (ALP, ALT and bilirubin) and renal (BUN and creatinine) functions. Based on observations, significant (p < 0.05) reduction in pain was noted in Group-II, III, and IV dogs. Using GFP, significant increases in peak vertical force (N/kg body wt) and impulse area (N s/kg body wt), indicative of a decrease in arthritis associated pain, were observed in Group-II dogs only. None of the dogs in any group showed changes in physical, hepatic or renal functions. In conclusion, based on GFP data, moderately arthritic dogs treated with UC-II (10 mg) showed a marked reduction in arthritic pain with maximum improvement by day 150. UC-II, GLU and CHO operate through different mechanisms of action, and were well tolerated over a period of 150 days.

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“…For instance, the synthesis/action of proinflammatory cytokines can be down-regulated by either antiinflammatory cytokines, the release of soluble receptors, or natural antagonists (14). In recent years, the family of nuclear receptors, including peroxisome proliferatoractivated receptor ␥ (PPAR␥), has generated particular interest because of its potential role in regulating the synthesis of a large number of catabolic factors involved in arthritis.…”

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confidence: 99%

The peroxisome proliferator–activated receptor γ agonist pioglitazone reduces the development of cartilage lesions in an experimental dog model of osteoarthritis: In vivo protective effects mediated through the inhibition of key signaling and catabolic pathways

Boileau

Martel‐Pelletier

Fahmi

et al. 2007

Arthritis & Rheumatism

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Objective. Emerging evidence indicates that peroxisome proliferator-activated receptor ␥ (PPAR␥) may have protective effects in osteoarthritis (OA). The aim of this study was to evaluate the in vivo effect of a PPAR␥ agonist, pioglitazone, on the development of lesions in a canine model of OA, and to explore the influence of pioglitazone on the major signaling and metabolic pathways involved in OA pathophysiologic changes.Methods. OA was surgically induced in dogs by sectioning of the anterior cruciate ligament. The dogs were then randomly divided into 3 treatment groups in which they were administered either placebo, 15 mg/day pioglitazone, or 30 mg/day pioglitazone orally for 8 weeks. Following treatment, the severity of cartilage lesions was scored. Cartilage specimens were processed for histologic and immunohistochemical evaluations; specific antibodies were used to study the levels of matrix metalloproteinase 1 (MMP-1), ADAMTS-5, and inducible nitric oxide synthase (iNOS), as well as phosphorylated MAPKs ERK-1/2, p38, JNK, and NF-B p65.Results. Pioglitazone reduced the development of cartilage lesions in a dose-dependent manner, with the highest dosage producing a statistically significant change (P < 0.05). This decrease in lesions correlated with lower cartilage histologic scores. In addition, pioglitazone significantly reduced the synthesis of the key OA mediators MMP-1, ADAMTS-5, and iNOS and, at the same time, inhibited the activation of the signaling pathways for MAPKs ERK-1/2, p38, and NF-B.Conclusion. These results indicate the efficacy of pioglitazone in reducing cartilage lesions in vivo. The results also provide new and interesting insights into a therapeutic intervention for OA in which PPAR␥ activation can inhibit major signaling pathways of inflammation and reduce the synthesis of cartilage catabolic factors responsible for articular cartilage degradation.Osteoarthritis (OA), one of the most common arthritic conditions, is primarily related to the progressive erosion of articular cartilage associated with synovial inflammation. The changes in cartilage are linked to a combination of mechanical and biochemical factors (1). The subchondral bone remodeling that takes place during the evolution of OA is believed to be an important factor in cartilage degradation (2-4). Its contribution seems to be associated with both the abnormal biophysical properties of the tissue and the excess synthesis of many catabolic factors, including growth hormones and cytokines, that can modulate the metabolism of OA cartilage (5-8).

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Cytokines and Growth Factors in the Treatment of Osteoarthritis: What Could be the Best Disease Modifying Drugs

Cited by 5 publications

References 154 publications

Suppressive Effect of the n‐Hexane Extract of Litsea japonica Fruit Flesh on Monosodium‐Iodoacetate‐Induced Osteoarthritis in Rats

Suppressive Effect of the n‐Hexane Extract of Litsea japonica Fruit Flesh on Monosodium‐Iodoacetate‐Induced Osteoarthritis in Rats

Comparative therapeutic efficacy and safety of type‐II collagen (uc‐II), glucosamine and chondroitin in arthritic dogs: pain evaluation by ground force plate

The peroxisome proliferator–activated receptor γ agonist pioglitazone reduces the development of cartilage lesions in an experimental dog model of osteoarthritis: In vivo protective effects mediated through the inhibition of key signaling and catabolic pathways

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