Low dose native type II collagen prevents pain in a rat osteoarthritis model

Mannelli, Lorenzo Di Cesare; Micheli, Laura; Zanardelli, Matteo; Ghelardini, Carla

doi:10.1186/1471-2474-14-228

Cited by 59 publications

(64 citation statements)

References 47 publications

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“…In animal studies, pain can be evaluated indirectly, using for instance weight bearing or gait analyses, or directly by assessing for instance paw withdrawal threshold in response to mechanical or thermal stimuli . We only tested one of these parameters, but it has been reported that a pain‐relieving substance has similar effects on multiple pain‐related outcome measures in a rat MIA OA model . Our findings show a decrease in pain, as measured by a significant increased weight bearing of the affected limb after intra‐articular application of MSCs.…”

Section: Discussionmentioning

confidence: 84%

Mesenchymal stem cells reduce pain but not degenerative changes in a mono-iodoacetate rat model of osteoarthritis

et al. 2014

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ABSTRACT:We studied the effects of intra-articularly injected bone marrow derived mesenchymal stem cells (MSCs), as well as freshly isolated bone marrow mononuclear cells (BMMNCs), on pain, cartilage damage, bone changes and inflammation in an in-vivo rat osteoarthritis (OA) model. OA was induced unilaterally by injection of mono-iodoacetate (MIA) and allowed to develop for 3 weeks. Then, animals were treated by intra-articular injection with MSCs, BMMNCs, or saline as a control. Four weeks later, pain was assessed with an incapitance tester, subchondral bone alterations were measured with mCT and cartilage quality and joint inflammation were assessed by histological analysis. Animals treated with MSCs distributed significantly more weight to the affected limb after treatment, which was not observed in the other groups. No statistically significant differences between treatment groups regarding cartilage damage, subchondral bone alterations and synovial inflammation were observed. Additional cell tracking experiments indicated adequate intra-articular cell injection and cell survival up to 2 weeks. In our OA model, injected MSCs were able to reduce MIA induced pain, as measured by an increased weight distribution to the affected limb. No statistically significant effects of the cellular therapies on structural damage and synovial inflammation were found. ß

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Section: Discussionmentioning

confidence: 84%

Mesenchymal stem cells reduce pain but not degenerative changes in a mono-iodoacetate rat model of osteoarthritis

et al. 2014

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“…The rats ( n = 6) receiving only the saline solution served as sham control animals (group I) throughout the experiment. The pain sensitivity of the knee joints was measured before MIA injection and once every week after MIA injection as described by Di Cesare et al [21]. The Pressure Application Measurement device (PAM; Ugo Basile, Italy) was used to measure the mechanical pain threshold of the knee joints.…”

Section: Methodsmentioning

confidence: 99%

Efficacy and safety of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (Stempeucel®): preclinical and clinical trial in osteoarthritis of the knee joint

et al. 2016

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BackgroundOsteoarthritis (OA) is a common and debilitating chronic degenerative disease of the joints. Currently, cell-based therapy is being explored to address the repair of damaged articular cartilage in the knee joint.MethodsThe in vitro differentiation potential of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (Stempeucel®) was determined by differentiating the cells toward the chondrogenic lineage and quantifying sulfated glycosaminoglycan (sGAG). The mono-iodoacetate (MIA)-induced preclinical model of OA has been used to demonstrate pain reduction and cartilage formation. In the clinical study, 60 OA patients were randomized to receive different doses of cells (25, 50, 75, or 150 million cells) or placebo. Stempeucel® was administered by intra-articular (IA) injection into the knee joint, followed by 2 ml hyaluronic acid (20 mg). Subjective evaluations—visual analog scale (VAS) for pain, intermittent and constant osteoarthritis pain (ICOAP), and Western Ontario and McMaster Universities Osteoarthritis (WOMAC-OA) index—were performed at baseline and at 1, 3, 6, and 12 months of follow-up. Magnetic resonance imaging of the knee was performed at baseline, and at 6 and 12 months follow-up for cartilage evaluation.ResultsStempeucel® differentiated into the chondrogenic lineage in vitro with downregulation of Sox9 and upregulation of Col2A genes. Furthermore, Stempeucel® differentiated into chondrocytes and synthesized a significant amount of sGAG (30 ± 1.8 μg/μg GAG/DNA). In the preclinical model of OA, Stempeucel® reduced pain significantly and also repaired damaged articular cartilage in rats. In the clinical study, IA administration of Stempeucel® was safe, and a trend towards improvement was seen in the 25-million-cell dose group in all subjective parameters (VAS, ICOAP, andWOMAC-OA scores), although this was not statistically significant when compared to placebo. Adverse events were predominant in the higher dose groups (50, 75, and 150 million cells). Knee pain and swelling were the most common adverse events. The whole-organ magnetic resonance imaging score of the knee did not reveal any difference from baseline and the placebo group.ConclusionIntra-articular administration of Stempeucel® is safe. A twenty-five-million-cell dose may be the most effective among the doses tested for pain reduction. Clinical studies with a larger patient population are required to demonstrate a robust therapeutic efficacy of Stempeucel® in OA.Trial registrationClinicaltrials.gov NCT01453738. Registered 13 October 2011.

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“…The first inflammatory phase (day 7 after MIA injection) is followed by an increasing neuropathic component leading to enhanced responses to normal or suprathreshold stimulation (allodynia-and hyperalgesia-related measurements; Di Cesare Mannelli et al, 2013b). On day 14, Capparis spinosa preparations relieved MIAdependent articular pain (both hypersensitivity and spontaneous pain) showing efficacy also against a predominantly neuropathic pain.…”

Section: Discussionmentioning

confidence: 99%

Acute effect of Capparis spinosa root extracts on rat articular pain

Maresca

Micheli

Mannelli

et al. 2016

Journal of Ethnopharmacology

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a b s t r a c tEthnopharmacological relevance: Capparis spinosa L. originates from dry regions of Asia and Mediterranean basin. In traditional medicine of these areas, infusions from caper root are considered to be beneficial for the treatment of rheumatism, gout and against abdominal pains. Aim of the study: To evaluate the pain relieving properties of a Syrian cultivar of Capparis spinosa roots in rat models of osteoarthritis and rheumatoid arthritis. Materials and methods: Decoction (DEC) and hydroalcoholic extract (EtH 2 O) were obtained from powdered roots; the latter was further separated in CH 2 Cl 2 and aqueous (H 2 O-Res) fractions. The extracts were characterized in terms of spermidine alkaloids by HPLC/DAD/MS and stachydrine by NMR. Different amount of free and glycosilated forms of capparispine and analogues (from 0.5% w/w for DEC up to 7.6% w/w for CH 2 Cl 2 fraction) were detected. Rat models of rheumatoid arthritis and osteoarthritis were induced by the intra-articular administration of Complete Freund's Adjuvant (CFA) or monosodium iodoacetate (MIA), respectively. Results: Fourteenth days after CFA or MIA injection, the different preparations of Capparis spinosa (3, 30, 100 and 300 mg kg À 1 ) were acutely administered p.o.. Powdered roots (300 mg kg ) significantly reduced hypersensitivity to mechanical noxious stimuli as well as spontaneous pain evaluated as hind limb bearing alterations in both models. The CH 2 Cl 2 and the H 2 O-Res (30 mg kg À 1 ) were the most potent in reverting pain threshold alterations despite the different content of free alkaloids. Conclusions: Capparis spinosa extracts relieved pain related to rheumatoid arthritis and osteoarthritis after single administration. A synergistic effect due to a specific "phytochemical mixture" is suggested.

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Low dose native type II collagen prevents pain in a rat osteoarthritis model

Cited by 59 publications

References 47 publications

Mesenchymal stem cells reduce pain but not degenerative changes in a mono-iodoacetate rat model of osteoarthritis

Mesenchymal stem cells reduce pain but not degenerative changes in a mono-iodoacetate rat model of osteoarthritis

Efficacy and safety of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (Stempeucel®): preclinical and clinical trial in osteoarthritis of the knee joint

Acute effect of Capparis spinosa root extracts on rat articular pain

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