Efficacy and safety of cannabidiol for the treatment of canine osteoarthritis: a systematic review and meta-analysis of animal intervention studies.

Introduction: Canine osteoarthritis (OA) is a degenerative disease with chronic inflammation of internal and external joint structures in dogs. Cannabis spp. contains cannabidiol (CBD), a substance known for various potential indications, such as pain relief and anti-inflammatory in various types of animals, including dogs with OA. As CBD is increasingly in the spotlight for medical use, we aimed to perform a systematic review and meta-analysis to evaluate the efficacy and safety of CBD in treating canine OA. Methods: We searched PubMed, Embase, Scopus, and CAB Direct for animal intervention studies investigating the effects of CBD for canine OA from database inception until February 28, 2023. Study characteristics and findings were summarized. A risk of bias in the included studies was assessed. Meta-analyses were performed using a random-effects model to estimate the effects of CBD on pain scores (0-10), expressed as mean difference (MD) and 95% confidence interval (95% CI). Certainty of evidence was assessed using GRADE. Results: Five articles were included, which investigated the effects of CBD in 117 dogs with OA. All studies were rated as having a high risk of bias. CBD products varied substantially, i.e., oral full-spectrum CBD oil in four studies, and isolated CBD oil and liposomal CBD oil in another study. Treatment duration varied from 4-12 weeks. Meta-analyses of three studies found that, in dogs with OA, treatment with oral full-spectrum CBD oil may reduce pain severity scores (MD; -0.60, 95% CI; -1.51 to 0.31, I2 = 45.64%, p = 0.19) and pain interference scores (MD; -1.52, 95% CI; -3.84 to 0.80, I2 = 89.59%, p = 0.20) but the certainty of evidence was very low. CBD is generally considered safe and well-tolerated in the short-run, with few mild adverse events observed, such as vomiting and asymptomatic increase in alkaline phosphatase level. Conclusion: CBD is considered safe for treating canine OA. CBD may reduce pain scores, but the evidence is very uncertain to conclude its clinical efficacy. High-quality clinical trials are needed to further evaluate the roles of CBD in canine OA.

Stimulation of Dentin Regeneration by Using Acemannan in Teeth with Lipopolysaccharide-induced Pulp Inflammation.

INTRODUCTION: This study investigated the effects of acemannan, a polysaccharide from Aloe vera, on human deciduous pulp cells in vitro and the response after vital pulp therapy in dog deciduous teeth. METHODS: Human primary dental pulpal cells were treated with acemannan in vitro and evaluated for proliferation, alkaline phosphatase activity, type I collagen, bone morphogenetic protein (BMP-2), BMP-4, vascular endothelial growth factor, and dentin sialoprotein expression and mineralization. Osteogenesis-related gene expression was analyzed by complementary DNA microarray. Pulpal inflammation was induced in dog teeth for 14 days. The inflamed pulp was removed, retaining the healthy pulp. The teeth were randomly divided into 3 treatment groups: acemannan, mineral trioxide aggregate, and formocresol. Sixty days later, the teeth were extracted and evaluated histopathologically. RESULTS: Acemannan significantly increased pulp cell proliferation, alkaline phosphatase, type I collagen, BMP-2, BMP-4, vascular endothelial growth factor, and dentin sialoprotein expression and mineralization approximately 1.4-, 1.6-, 1.6-, 5.5-, 2.6-, 3.8-, 1.8-, and 4.8-fold, respectively, compared with control. In vivo, partial pulpotomy treatment using acemannan generated outcomes similar to mineral trioxide aggregate treatment, resulting in mineralized bridge formation with normal pulp tissue without inflammation or pulp necrosis. In contrast, the formocresol group demonstrated pulp inflammation without mineralized bridge formation. CONCLUSIONS: Acemannan is biocompatible with the dental pulp. Furthermore, acemannan stimulated dentin regeneration in teeth with reversible pulpitis.

Localized delivery of curcumin from injectable gelatin/Thai silk fibroin microspheres for anti-inflammatory treatment of osteoarthritis in a rat model.

The previously developed gelatin/silk fibroin microspheres were loaded with curcumin and applied for anti-inflammatory treatment in monosodium iodoacetate (MIA)-induced osteoarthritis (OA) in a rat model. The MIA-induced OA rats received a single intra-articular injection with gelatin or gelatin/silk fibroin (30/70) microspheres encapsulating curcumin. The therapeutic effects of treatment groups [concentration of interleukin-6 (IL-6) in blood serum, radiographic and the histological grading on articular joint] were compared with those of normal saline treated OA and normal rats. The result showed that both microsphere groups reduced the level of IL-6 in serum after 1 week of treatment. The gelatin/silk fibroin (30/70) microspheres encapsulating curcumin delayed the cellular destruction in articular joint and synovial tissue after 8 weeks. The radiographic and histological gradings on articular cartilage lesion and synovial tissue change of rats treated with gelatin/silk fibroin (30/70) microspheres encapsulating curcumin were close to those of the normal rats. It was explained that the slow-degrading gelatin/silk fibroin (30/70) microspheres released curcumin for extended period and showed a prolonged anti-inflammatory effect, compared to the fast-degrading gelatin microspheres. This delivery system of curcumin was suggested to be applied for localized treatment of anti-inflammatory in OA with minimal invasion.

Effects of different omega-3 sources, fish oil, krill oil, and green-lipped mussel against cytokine-mediated canine cartilage degradation.

Our purpose was to evaluate the protective effect of three marine omega-3 sources, fish oil (FO), krill oil (KO), and green-lipped mussel (GLM) against cartilage degradation. Canine cartilage explants were stimulated with either 10 ng/mL interleukin-1ß (IL-1ß) or IL-1ß/oncostatin M (10 ng/mL each) and then treated with various concentrations of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA; 3 and 30 µg/mL), FO, KO, or GLM (250, 500, and 1000 µg/mL) for 28 days. Gene expression was then investigated in primary canine chondrocytes. Our results showed that DHA and EPA as well as omega-3 sources could suppress matrix degradation in cytokine-induced cartilage explants by significantly reducing the increase of sulfated glycosaminoglycans (s-GAGs) and preserving uronic acid and hydroxyproline content (except GLM). These agents were not able to reduce IL-1ß-induced IL1B and TNFA expression but were able to down-regulate the expression of the catabolic genes MMP1, MMP3, and MMP13 and up-regulate the anabolic genes AGG and COL2A1; FO and KO were especially effective. Our findings indicated that FO and KO were superior to GLM for their protective effect against proteoglycan and collagen degradation. Hence, FO and KO could serve as promising sources of chondroprotective agents.