The Effect of Probiotics on the Management of Pain and Inflammation in Osteoarthritis: A Systematic Review and Meta-Analysis of Clinical Studies.

Osteoarthritis (OA) is one of the most common musculoskeletal disorders. Recently, research has focused on the role of intestinal microbiome dysbiosis in OA. The aim of this study was to systematically review randomized intervention clinical studies investigating the effect of probiotics on the management of OA-related pain and inflammation.

Classical cannabinoid receptors as target in cancer-induced bone pain: a systematic review, meta-analysis and bioinformatics validation.

To test the hypothesis that genetic and pharmacological modulation of the classical cannabinoid type 1 (CB) and 2 (CB) receptors attenuate cancer-induced bone pain, we searched Medline, Web of Science and Scopus for relevant skeletal and non-skeletal cancer studies from inception to July 28, 2022. We identified 29 animal and 35 human studies. In mice, a meta-analysis of pooled studies showed that treatment of osteolysis-bearing males with the endocannabinoids AEA and 2-AG (mean difference [MD] - 24.

The Role of Nutrition in Osteoarthritis Development.

Osteoarthritis (OA) prevalence has increased 113% since 1990, and currently more than half a billion people worldwide are living with this slowly progressing, degenerative joint disease [...

TRAF6 as a potential target in advanced breast cancer: a systematic review, meta-analysis, and bioinformatics validation.

TRAF6 has emerged as a key regulator of breast cancer (BCa). However, the TRAF family constitutes of seven members that exhibit distinct and overlapping functions. To explore which TRAF represents a potential druggable target for BCa treatment, we searched Medline, Web of Science and Scopus for relevant studies from inception to June 27, 2021.

Effects of zoledronic acid on osteosarcoma progression and metastasis: systematic review and meta-analysis.

Zoledronic Acid (ZA) has been shown to inhibit Osteosarcoma (OSA) progression in preclinical studies. However, the use of ZA as an intervention for OSA treatment and management remains controversial. A systematic review and meta-analysis of randomized-controlled trials comparing the use of ZA with standard treatment vs.

Probiotics Inhibit Cartilage Damage and Progression of Osteoarthritis in Mice.

Increasing interest has focussed on the possible role of alterations in the microbiome in the pathogenesis of metabolic disease, inflammatory disease, and osteoporosis. Here we examined the role of the microbiome in a preclinical model of osteoarthritis in mice subjected to destabilisation of medical meniscus (DMM). The intestinal microbiome was depleted by broad-spectrum antibiotics from 1 week before birth until the age of 6 weeks when mice were subjected reconstitution of the microbiome with faecal microbial transplant (FMT) followed by the administration of a mixture of probiotic strains Lacticaseibacillus paracasei 8700:2, Lactiplantibacillus plantarum HEAL9 and L.

Dexamethasone Administration in Mice Leads to Less Body Weight Gain over Time, Lower Serum Glucose, and Higher Insulin Levels Independently of NRF2.

Glucocorticoids are used widely on a long-term basis in autoimmune and inflammatory diseases. Their adverse effects include the development of hyperglycemia and osteoporosis, whose molecular mechanisms have been only partially studied in preclinical models. Both these glucocorticoid-induced pathologies have been shown to be mediated at least in part by oxidative stress.

Toscana virus encephalitis in Southwest Germany: a retrospective study.

Background: Toscana virus (TOSV) is an arthropod-borne virus transmitted by phlebotomine sandflies (Phlebotomus sp.) widespread throughout the Mediterranean having the potential to cause meningoencephalitis in humans. In Germany, the vectors of TOSV are introduced recently and become endemic especially in Southwestern Germany.

Anti-inflammatory, but not osteoprotective, effect of the TRAF6/CD40 inhibitor 6877002 in rodent models of local and systemic osteolysis.

NFκB plays a key role in inflammation and skeletal disorders. Previously, we reported that pharmacological inhibition of NFκB at the level of TRAF6 suppressed RANKL, CD40L and IL1β-induced osteoclastogenesis and attenuated cancer-induced bone disease. TNFα is also known to regulate TRAF6/NFκB signalling, however the anti-inflammatory and osteoprotective effects associated with inhibition of the TNFα/TRAF6/NFκB axis have not been investigated.

Association of cannabinoid receptor modulation with normal and abnormal skeletal remodelling: A systematic review and meta-analysis of in vitro, in vivo and human studies.

To address the inconsistent findings from studies that used different models to explore the role of classical cannabinoid type 1 (CB1) and 2 (CB2) receptors in skeletal remodelling, we searched Medline, Web of Science and Embase for relevant studies from inception to June 23, 2020. We identified 38 in vitro, 34 in vivo and 9 human studies. A meta-analysis of in vitro studies showed that exposure to the inverse-agonists AM251 (mean difference [MD]:-26.

Targeted Inactivation of Rin3 Increases Trabecular Bone Mass by Reducing Bone Resorption and Favouring Bone Formation.

Common genetic variants at the RIN3 locus on chromosome 14q32 predispose to Paget's disease of bone (PDB) but the mechanisms by which they do so are unknown. Here, we analysed the skeletal phenotype of female mice with targeted inactivation of the mouse Rin3 gene (Rin3) as compared with wild-type littermates. The Rin3 mice had higher trabecular bone volume (BV/TV%) compared with wild type.

JZL184, A Monoacylglycerol Lipase Inhibitor, Induces Bone Loss in a Multiple Myeloma Model of Immunocompetent Mice.

Multiple myeloma (MM) patients develop osteolysis characterised by excessive osteoclastic bone destruction and lack of osteoblast bone formation. Pharmacological manipulation of monoacylglycerol lipase (MAGL), an enzyme responsible for the degradation of the endocannabinoid 2-arachidonoyl glycerol (2-AG), reduced skeletal tumour burden and osteolysis associated with osteosarcoma and advanced breast and prostate cancers. MM and hematopoietic, immune and bone marrow cells express high levels of type 2 cannabinoid receptor and osteoblasts secrete 2-AG.

Conditional deletion of E11/Podoplanin in bone protects against ovariectomy-induced increases in osteoclast formation and activity.

E11/Podoplanin (Pdpn) is implicated in early osteocytogenesis and the formation of osteocyte dendrites. This dendritic network is critical for bone modelling/remodelling, through the production of receptor activator of nuclear factor κ B (RANK)-ligand (RANKL). Despite this, the role of Pdpn in the control of bone remodelling is yet to be established in vivo.

Liver-derived IGF-I is not required for protection against osteoarthritis in male mice.

Insulin-like growth factor-I (IGF-I) is anabolic for cartilage and important for cartilage integrity, which might suggest a connection between IGF-I and osteoarthritis (OA) development. However, the results of studies performed so far are conflicting, and we aimed to clarify the role of endocrine IGF-I in rodent OA. Male mice with inducible inactivation of circulating, liver-derived IGF-I (LI-IGF-I mice, serum IGF-I reduced by ~80%) were used.

Paradoxical effects of JZL184, an inhibitor of monoacylglycerol lipase, on bone remodelling in healthy and cancer-bearing mice.

Background: Cancer-associated bone disease is a serious complication in bone sarcomas and metastatic carcinomas of breast and prostate origin. Monoacylglycerol lipase (MAGL) is an enzyme of the endocannabinoid system, and is responsible for the degradation of the most abundant endocannabinoid in bone, 2-arachidonoyl glycerol (2AG).

Methods: The effects of the verified MAGL inhibitor on bone remodelling were assessed in healthy mice and in mouse models of bone disease caused by prostate and breast cancers and osteosarcoma.

Raman spectroscopy as a predictive tool for monitoring osteoporosis therapy in a rat model of postmenopausal osteoporosis.

Pharmacological therapy of osteoporosis reduces bone loss and risk of fracture in patients. Modulation of bone mineral density cannot explain all effects. Other aspects of bone quality affecting fragility and ways to monitor them need to be better understood.

Osteoarthritis Mouse Model of Destabilization of the Medial Meniscus.

This chapter describes the surgical procedure for destabilization of medial meniscus in mice. Details on subsequent microCT and histological analysis are also provided, as well as details on osteoarthritis evaluation.

Ovariectomy/Orchiectomy in Rodents.

This chapter describes the surgical procedures for ovariectomy and orchiectomy in mice and rats. In addition to providing technical details of the surgical techniques, details of anesthesia options and pre-, peri-, and postoperative care are also included.

Analysis of Transcriptional Regulation in Bone Cells.

Transcription is a process by which the rate of RNA synthesis is regulated. Here we describe the techniques for carrying out promoter-reporter assays, electrophoretic mobility shift assays, chromosome conformation capture (3C) assays, chromatin immunoprecipitation assays, and CRISPR-Cas9 assay, five commonly used methods for studying and altering gene transcription.

Regulation of breast cancer induced bone disease by cancer-specific IKKβ.

NFκB is implicated in breast cancer bone metastasis and skeletal remodelling. However, the role of IKKβ, a key component of the canonical NFκB pathway, in the regulation of breast cancer osteolytic metastasis has not been investigated. Here, we describe the cancer-specific contribution of IKKβ to bone metastasis, skeletal tumour growth and osteolysis associated with breast cancer.

Raman spectroscopy predicts the link between claw keratin and bone collagen structure in a rodent model of oestrogen deficiency.

Osteoporosis is a common disease characterised by reduced bone mass and an increased risk of fragility fractures. Low bone mineral density is known to significantly increase the risk of osteoporotic fractures, however, the majority of non-traumatic fractures occur in individuals with a bone mineral density too high to be classified as osteoporotic. Therefore, there is an urgent need to investigate aspects of bone health, other than bone mass, that can predict the risk of fracture.

Combined deficiency of the Cnr1 and Cnr2 receptors protects against age-related bone loss by osteoclast inhibition.

The endocannabinoid system plays a role in regulating bone mass and bone cell activity and inactivation of the type 1 (Cnr1) or type 2 (Cnr2) cannabinoid receptors influences peak bone mass and age-related bone loss. As the Cnr1 and Cnr2 receptors have limited homology and are activated by different ligands, we have evaluated the effects of combined deficiency of Cnr1 and 2 receptors (Cnr1/2 ) on bone development from birth to old age and studied ovariectomy induced bone loss in female mice. The Cnr1/2 mice had accelerated bone accrual at birth when compared with wild type littermates, and by 3 months of age, they had higher trabecular bone mass.

Heavy Cannabis Use Is Associated With Low Bone Mineral Density and an Increased Risk of Fractures.

Purpose: To investigate possible associations between recreational cannabis use and bone health in humans.

Methods: Cross-sectional study of individuals recruited from primary care in the UK between 2011 and 2013. Cases were regular smokers of cannabis divided into moderate (n = 56) and heavy user (n = 144) subgroups depending on whether they reported fewer or more than 5000 cannabis smoking episodes during their lifetime.