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ID PMID Title PublicationDate abstract
33042107 The Emerging Role of Neutrophil Extracellular Traps (NETs) in Tumor Progression and Metast 2020 Neutrophil Extracellular Traps (NETs) are net-like structures composed of DNA-histone complexes and proteins released by activated neutrophils. In addition to their key role in the neutrophil innate immune response, NETs are also involved in autoimmune diseases, like systemic lupus erythematosus, rheumatoid arthritis, psoriasis, and in other non-infectious pathological processes, as coagulation disorders, thrombosis, diabetes, atherosclerosis, vasculitis, and cancer. Recently, a large body of evidence indicates that NETs are involved in cancer progression and metastatic dissemination, both in animal models and cancer patients. Interestingly, a close correlation between cancer cell recruitment of neutrophils in the tumor microenvironment (Tumor Associated Neutrophils. TANs) and NET formation has been also observed either in primary tumors and metastatic sites. Moreover, NETs can also catch circulating cancer cells and promote metastasis. Furthermore, it has been reported that wake dormant cancer cells, causing tumor relapse and metastasis. This review will primarily focus on the pro-tumorigenic activity of NETs in tumors highlighting their ability to serve as a potential target for cancer therapy.
33005175 Systematic Transcriptome Analysis of Noise-Induced Hearing Loss Pathogenesis Suggests Infl 2020 Noise-induced hearing loss (NIHL) is characterized by damage to cochlear neurons and associated hair cells; however, a systematic evaluation of NIHL pathogenesis is still lacking. Here, we systematically evaluated differentially expressed genes of 22 cochlear samples in an NIHL mouse model. We performed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and weighted gene co-expression network analysis (WGCNA). Core modules were detected using protein-protein interactions and WGCNA with functional annotation, diagnostic value evaluation, and experimental validation. Pooled functional annotation suggested the involvement of multiple inflammatory pathways, including the TNF signaling pathway, IL-17 signaling pathway, NF-kappa B signaling pathway, rheumatoid arthritis, and p53 signaling pathway. The core modules suggested that responses to cytokines, heat, cAMP, ATP, mechanical stimuli, and immune responses were important in NIHL pathogenesis. These activities primarily occurred on the external side of the plasma membrane, the extracellular region, and the nucleus. Binding activities, including CCR2 receptor binding, protein binding, and transcription factor binding, may be important. Additionally, the hub molecules with diagnostic value included Relb, Hspa1b, Ccl2, Ptgs2, Ldlr, Plat, and Ccl17. An evaluation of Relb and Hspa1b protein levels showed that Relb was upregulated in spiral ganglion neurons, which might have diagnostic value. In conclusion, this study indicates that the inflammatory response is involved in auditory organ changes in NIHL pathogenesis; moreover, several molecules and activities have essential and subtle influences that have translational potential for pharmacological intervention.
32802941 Nephrotoxicity Associated with Low-dose Methotrexate and Outpatient Parenteral Microbial T 2020 Methotrexate (MTX) toxicity can affect multiple organ systems, manifesting as nephrotoxicity, myelosuppression, hepatotoxicity, mucositis, and gastrointestinal upset. Serious adverse events are rare in patients prescribed low-dose methotrexate. We present a case of an 86-year-old female on a weekly dose of oral MTX 12.5 mg for rheumatoid arthritis presenting with painful gingiva and oral bleeding during outpatient antimicrobial therapy (OPAT) for osteomyelitis with vancomycin and piperacillin-tazobactam. She had acute kidney injury (AKI), elevated serum MTX levels, thrombocytopenia, neutropenia, and a vancomycin level three times therapeutic concentration. MTX toxicity was suspected to have been triggered by vancomycin and piperacillin-tazobactam causing AKI and impaired renal clearance of MTX which itself is nephrotoxic. The patient was managed with leucovorin, alkalinized intravenous fluids, and filgrastim injections over a 2-week period. Her renal function continued to be reduced at 5-week outpatient follow-up, far after other markers of toxicity normalized. This case demonstrates the importance of considering potential drug-drug interactions and the need for robust monitoring for OPAT in select groups.
32743515 The immunobiology of humanized Anti-IL6 receptor antibody: From basic research to breakthr 2020 The clinical use of monoclonal antibodies is well established in human medicine and has been amongst the most important contributions of basic science to clinical disease. One such antibody, the humanized anti-human IL-6 receptor antibody, is used to treat a variety of autoimmune diseases, particularly rheumatoid arthritis. It is extremely difficult and a laborious process to go from a concept at the research bench, to government approval. Such approval implies not only efficacy but, more importantly, an appropriate safety profile. In this review, the history of anti-human IL-6 receptor antibody is discussed in depth beginning with the author's experience during a sabbatical visit at the University of California at Davis in 1978. At that time, it was discovered that B cell activation was at least one critical factor in the development of autoimmunity. Approximately six years later, the cDNA encoding for IL-6 was cloned as BSF-2 (B cell stimulatory factor 2) to differentiate B cells to produce antibody. Soon after, it was suggested that this cytokine plays an important role in the development of autoimmune diseases. Based on this evidence, the journey began to search for an IL-6 inhibitor. Although there were numerous obstacles in finding lead compounds, ultimately, basic science developed the methodology for high throughput readouts that would inhibit the biologic function of IL-6. It was finally concluded that a mouse monoclonal antibody against IL-6 receptor would be optimal. In 1991, this antibody was humanized by using CDR-grafting technology in collaboration with the MRC (Medical Research Council). The drug was named tocilizumab and launched as an innovative anti-rheumatic drug in 2008 in Japan. Subsequently, the drug has been used throughout the world and has achieved enormous success in helping patients who suffer from inflammatory arthropathies. The lessons learned in the development of this antibody have application to the study of biologics and their application to other human diseases.
32711378 Type III intermediate filaments as targets and effectors of electrophiles and oxidants. 2020 Sep Intermediate filaments (IFs) play key roles in cell mechanics, signaling and homeostasis. Their assembly and dynamics are finely regulated by posttranslational modifications. The type III IFs, vimentin, desmin, peripherin and glial fibrillary acidic protein (GFAP), are targets for diverse modifications by oxidants and electrophiles, for which their conserved cysteine residue emerges as a hot spot. Pathophysiological examples of these modifications include lipoxidation in cell senescence and rheumatoid arthritis, disulfide formation in cataracts and nitrosation in endothelial shear stress, although some oxidative modifications can also be detected under basal conditions. We previously proposed that cysteine residues of vimentin and GFAP act as sensors for oxidative and electrophilic stress, and as hinges influencing filament assembly. Accumulating evidence indicates that the structurally diverse cysteine modifications, either per se or in combination with other posttranslational modifications, elicit specific functional outcomes inducing distinct assemblies or network rearrangements, including filament stabilization, bundling or fragmentation. Cysteine-deficient mutants are protected from these alterations but show compromised cellular performance in network assembly and expansion, organelle positioning and aggresome formation, revealing the importance of this residue. Therefore, the high susceptibility to modification of the conserved cysteine of type III IFs and its cornerstone position in filament architecture sustains their role in redox sensing and integration of cellular responses. This has deep pathophysiological implications and supports the potential of this residue as a drug target.
32670246 Denosumab Regulates Gut Microbiota Composition and Cytokines in Dinitrobenzene Sulfonic Ac 2020 The pro-inflammatory mediator receptor activator of nuclear factor-kappa B ligand (RANKL) plays a significant role in the development of rheumatoid arthritis; however, its role in inflammatory bowel disease is unknown. Genome-wide association meta-analysis for Crohn's disease (CD) identified a variant near the TNFSF11 gene that encodes RANKL and CD risk allele increased expression of RANKL in specific cell lines. This study aims to elucidate if the RANKL inhibitor denosumab can reduce the severity of experimental colitis and modify the gut microbiota composition using murine dinitrobenzenesulfonic acid (DNBS)-experimental model of colitis mimicking CD. In colitic conditions, denosumab treatment significantly decreased the pro-inflammatory cytokines IL-6, IL-1β, and TNF-α within the colonic mucosa. Moreover, colitis was accompanied by disruption of gut microbiota, and preventative treatment with denosumab modulated this disruption. Denosumab treatment also modified the alpha- and beta diversity of colonic mucosa and fecal microbiota. These results provide a rationale for considering denosumab as a future potential therapy in CD; however, more detailed experimental and clinical studies are warranted.
32615604 [Inflammatory Muscle Pain: Polymyalgia Rheumatica with or without Large Vessel Vasculiti 2020 Jul Polymyalgia rheumatica (PMR) is characterized by rapidly evolving shoulder and pelvic girdle pain with fatigue, weight loss, night sweats and elevated CRP and ESR. Giant cell arteritis (GCA) can occur in PMR and vice versa. Headache and scalp tenderness are typical for GCA. GCA may be complicated by visual loss or by strokes.Imaging, particularly ultrasound, is helpful for distinguishing PMR from similar conditions such as shoulder osteoarthritis, rheumatoid arthritis and chondrocalcinosis. Subdeltoid bursitis, biceps tenosynovitis and hip joint effusions are common in PMR. The diagnosis of GCA needs to be either confirmed by imaging or by histology. Ultrasound is the imaging method of choice provided that expertise and adequate equipment are available. Inflamed arteries exhibit a concentric wall thickening. Patients with extracranial GCA are younger, more often female. Vasculitis commonly involves the aorta, subclavian arteries, axillary arteries and other arteries. The diagnosis of extracranial GCA may be confirmed by ultrasound, CT, MRI or PET.Prednisolone with a starting dose of 15-25 mg/d for PMR and of 40-60 mg/d for GCA results in rapid improvement of symptoms. Fast-track clinics provide clinical and ultrasound examinations by experts within 24 hours. Their introduction led to a decrease of visual loss in GCA. The prednisolone dose can be discontinued within 1 year in about 50 % of GCA patients. Additional treatment with tocilizumab allows to reduce flares and decrease glucocorticoid doses. Tocilizumab is particularly useful in patients with relapses and with increased risk of glucocorticoid side effects.
32211437 Population-based survey of antimycobacterial drug use among patients with non-tuberculosis 2020 Jan This report shows poor adherence to the recommended treatment regimen for NTM-PD patients, which may pose a potential risk for the development of macrolide resistance. The risk was highest among elderly patients, and those with rheumatoid arthritis and COPD. http://bit.ly/3aBoUzE.
32070175 New insights into the novel anti-inflammatory mode of action of glucocorticoids. 2020 Apr Inflammation is a physiological intrinsic host response to injury meant for removal of noxious stimuli and maintenance of homeostasis. It is a defensive body mechanism that involves immune cells, blood vessels and molecular mediators of inflammation. Glucocorticoids (GCs) are steroidal hormones responsible for regulation of homeostatic and metabolic functions of body. Synthetic GCs are the most useful anti-inflammatory drugs used for the treatment of chronic inflammatory diseases such as asthma, chronic obstructive pulmonary disease (COPD), allergies, multiple sclerosis, tendinitis, lupus, atopic dermatitis, ulcerative colitis, rheumatoid arthritis and osteoarthritis whereas, the long term use of GCs are associated with many side effects. The anti-inflammatory and immunosuppressive (desired) effects of GCs are usually mediated by transrepression mechanism whereas; the metabolic and toxic (undesired) effects are usually manifested by transactivation mechanism. Though GCs are most potent anti-inflammatory and immunosuppressive drugs, the common problem associated with their use is GC resistance. Several research studies are rising to comprehend these mechanisms, which would be helpful in improving the GC resistance in asthma and COPD patients. This review aims to focus on identification of new drug targets in inflammation which will be helpful in the resolution of inflammation. The ample understanding of GC mechanisms of action helps in the development of novel anti-inflammatory drugs for the treatment of inflammatory and autoimmune disease with reduced side effects and minimal toxicity.
32011425 Incorporating Prescription Drugs Into Affordable Care Act Risk Adjustment. 2020 Jun BACKGROUND: The 2010 Patient Protection and Affordable Care Act reformed the individual and small group health insurance markets and established a risk adjustment program to create a level playing field for competition. A new set of predictive models for measuring enrollee risk across plans was developed for the Patient Protection and Affordable Care Act-reformed markets, referred to as the Department of Health and Human Services Hierarchical Condition Category (HHS-HCC) models. Beginning in 2018, selected prescription drug classes were added to the models as risk markers. OBJECTIVE: We describe the motivations, concerns, methodology, and results of adding prescription drug utilization to the HHS-HCC models. METHODS: Separate HHS-HCC models are estimated by enrollee age and plan actuarial value. We defined and added 10 prescription drug classes, called RXCs, to the HHS-HCC adult models. RESULTS: Using selected RXCs alongside demographic and diagnostic indicators yielded modest overall improvement in HHS-HCC models' predictive power. Also, adding RXCs captures the higher costs of enrollees taking certain expensive pharmaceuticals and allows imputation of diagnoses for enrollees utilizing a drug but lacking the associated diagnosis. CONCLUSIONS: Including selected drugs in risk adjustment improved the models' predictive power. In addition, inclusion of selected drugs may discourage insurers from using formulary and drug benefit design to avoid enrollment of patients taking high-cost drugs, such as for HIV, multiple sclerosis, and rheumatoid arthritis, and improve access for enrollees taking these drugs. Adding RXCs also may improve plan risk measurement for plans with less complete diagnosis reporting.
31908308 Immune checkpoint inhibitors and tuberculosis: an old disease in a new context. 2020 Jan Tuberculosis, the leading cause of infection-related death in developing regions, is a leading cause of morbidity and mortality worldwide. Screening for, and treatment of, latent Mycobacterium tuberculosis infection is routine before initiation of anti-tumour necrosis factor α (anti-TNFα) agents in the management of psoriasis, Crohn's disease, and rheumatoid arthritis. By contrast, screening for latent tuberculosis before immune checkpoint inhibitor treatment in cancer is not routine, despite the increasing number of reports of primary infection with M tuberculosis or reactivation of latent M tuberculosis infection during such treatment. We present our experience with M tuberculosis screening in 70 patients who underwent immune checkpoint inhibitor therapy for metastatic skin cancer. Based on our understanding of the interaction between M tuberculosis and the immune system, we present the argument for tuberculosis screening before immune checkpoint inhibitor therapy and its use when considering anti-TNFα treatment for severe immune-related adverse events. We call for increased vigilance during immune checkpoint inhibition until its effects on tuberculosis pathophysiology are fully ascertained.
31801160 Evaluation of Phytochemical and Pharmacological Activity of Carissa carandas L. Fruits at 2020 Feb Inflammation plays an important role in various diseases with high prevalence within populations such as rheumatoid arthritis, ulcer, atherosclerosis and asthma. Many drugs are available in the market for inflammatory diseases but they exhibit several unwanted side effects. Therefore, alternative treatments with safer compounds are needed. The plant Carissa carandas L. plant is used traditionally for the treatment of various diseases. Hence to validate its traditional use, the present study has envisaged screening different solvents extract of Carissa carandas fruit for their phytochemical and pharmacological activity especially the anti-inflammatory activity of the fruits at 3 different stages of maturation. The n-hexane and chloroform extracts of immature, mature and ripe fruits showed positive tests for steroids and triterpenoids, whereas acetone extract showed positive tests for steroids, triterpenoids, alkaloids, tannins, sugar, saponins except for triterpenoids in immature fruits. The hydroalcoholic extract showed presence of alkaloids, tannins, sugars, saponin and flavonoids. The highest concentration of phenol, flavonoids and ascorbic acid were found to be more in acetone extract of mature fruits and of carbohydrates in ripe fruits. The hydroalcoholic extract also exhibited similar pattern. The anti-inflammatory property was evaluated by using different models like carrageenan induced paw edema in Wistar rats and cotton pellets induced granuloma. There was a consistent increase in % inhibition of inflammation at concentrations of 100 and 200 mg/kg up to 3 h. The highest activity was at 3 h with 200 mg/kg dose. Thus the present work has clearly proved that the acetone extract of mature fruits have considerable anti-inflammatory activity.
31502171 Microbiome as an Immunological Modifier. 2020 Humans are living ecosystems composed of human cells and microbes. The microbiome is the collection of microbes (microbiota) and their genes. Recent breakthroughs in the high-throughput sequencing technologies have made it possible for us to understand the composition of the human microbiome. Launched by the National Institutes of Health in USA, the human microbiome project indicated that our bodies harbor a wide array of microbes, specific to each body site with interpersonal and intrapersonal variabilities. Numerous studies have indicated that several factors influence the development of the microbiome including genetics, diet, use of antibiotics, and lifestyle, among others. The microbiome and its mediators are in a continuous cross talk with the host immune system; hence, any imbalance on one side is reflected on the other. Dysbiosis (microbiota imbalance) was shown in many diseases and pathological conditions such as inflammatory bowel disease, celiac disease, multiple sclerosis, rheumatoid arthritis, asthma, diabetes, and cancer. The microbial composition mirrors inflammation variations in certain disease conditions, within various stages of the same disease; hence, it has the potential to be used as a biomarker.
31389299 Probing the structural interactions between methotrexate and dexamethasone with muscle cys 2020 Jul Drug protein interactions have gained considerable attention over the past many years. In the current communication the association of muscle cystatin (MC) with anti-rheumatic drugs methotrexate and dexamethasone was studied by thiol proteinase inhibitor assay, ultra violet (UV) absorption, fluorescence spectroscopy, and fluorescence transform infra-red spectroscopy (FTIR). A static pattern of quenching was noticed between muscle cystatin and methotrexate (MTX). Binding constant (K(a)) of methotrexate to muscle cystatin was found to be 1 × 10(-7) M(-1) and the stoichiometry of binding was calculated to be one. Fluorescence measurement of the emission quenching reveals that the quenching process of cystatin by dexamethasone (DXN) was also static. The stoichiometry of binding and binding constant was also obtained. Additional evidence regarding MTX-MC and DXN-MC was obtained from UV spectroscopy and FTIR spectroscopic results. Such spectroscopic studies would help in modelling new candidate drugs for rheumatoid arthritis based on their cystatin binding profile.Communicated by Ramaswamy H. Sarma.
30963980 Novel Coupled Molecules from Active Structural Motifs of Synthetic and Natural Origin as I 2020 INTRODUCTION: Nitric oxide (NO) is an important mediator in the pathogenesis and control of immune system-related disorders and its levels are modulated by inducible NO synthase (iNOS). Oxidative stress is another pathological indication in majority of autoimmune disorders. The present study aims at the development of coupled molecules via selection of pharmacophores for both immunomodulatory and antioxidant activities through iNOS inhibition. METHODS: Variedly substituted coumarin moieties are coupled with naturally occurring phenols through an amide linkage and were predicted for activities using computer-based program PASS. The compounds predicted to have dual activities were synthesized. Docking studies were carried out against iNOS (PDB 1R35) and compounds having good docking score were evaluated for immunomodulatory and antioxidant activities. RESULTS: The synthesized compounds were found to be pure and were obtained in good yields. Compounds with maximum docking score (YR1a, YR2e, YR2c and YR4e) were selected for evaluation by in vitro models. Compounds YR2e and YR2c markedly inhibited the reduction of NBT dye and showed maximum % iNOS inhibition. In DPPH assay, compound YR4e was observed as the most potent antioxidant (EC50 0.33 µM/mL). Based on these studies, compounds YR2e and YR2c were selected for haemagglutination test. Compound YR2e was observed as the most active immunosuppressant with maximal inhibitory ability of iNOS and NBT reduction and lower HAT value of 3.5. CONCLUSION: Compound YR2e can be utilized as a pharmacological agent in the prevention or treatment of immunomodulatory diseases such as tumors, rheumatoid arthritis, ulcerative colitis, organ transplant and other autoimmune disorders.
33898698 The possible role of oral microbiome in autoimmunity. 2020 Dec OBJECTIVE: The human microbiome refers to the entire habitat, including microorganisms, their genomes and the surrounding environmental conditions of the microbial ecosystem. When the equilibrium between microbial habitats and host is disturbed, dysbiosis is caused. The oral microbiome (OMB) has been implicated in the manifestation of many intra- and extraoral diseases. Lately, there has been an intense effort to investigate and specify the relationship between microbial complexes, especially that of the oral cavity and intestine and autoimmunity. This study aimed to review the current literature about the possible role of the OMB in the pathogenesis of autoimmune diseases. METHODS: We searched for published articles in English indexed in PubMed, Medline, Research Gate and Google Scholar using a search strategy that included terms for oral microbiome, autoimmune diseases, dysbiosis and next-generation sequencing. RESULTS: An important number of articles were gathered and used for the description of the possible impact of dysbiosis of OMB in the pathogenesis of Sjögren's syndrome, systemic lupus erythematosus, rheumatoid arthritis, Behcet's disease, Crohn's disease and psoriasis. CONCLUSION: This review article draws attention to the relationship between OMB and the triggering of a number of autoimmune diseases. Although this specific topic has been previously reviewed, herein, the authors review recent literature regarding the full list of nosological entities related to the OMB, point out the interaction between the microbiome and sex hormones with regard to their role in autoimmunity and discuss novel and promising therapeutic approaches for systemic autoimmune diseases. Furthermore, the question arises of whether the OMB is associated with oral bullous autoimmune diseases.
33422443 The Association of Gastrocnemius Tightness, Genu Valgum and Hallux Valgus: A Prospective C 2021 Mar There has been much debate regarding the aetiology and pathogenesis of hallux valgus and it appears to be multifactorial with contracture or tightness of the Achilles tendon and more specifically the gastrocnemius being implicated as an intrinsic factor. The purpose of this study was to look at the association of gastrocnemius tightness, genu valgum and hallux valgus. A prospective case-control study with 25 patients in each group was carried out over a 12-month period. The case group observed adult patients who were referred primarily because of symptomatic hallux valgus and were assessed for the following: hallux valgus stage; presence or absence of isolated gastrocnemius tightness; presence or absence of genu valgum. The control group excluded those with pre-existing hallux valgus, genu valgum and rheumatoid arthritis and were assessed for isolated gastrocnemius tightness. There was a statistically significant association between the presence of genu valgum and hallux valgus when comparing both groups with a p < .001. There was also a statistically significant association between the Silfverskiöld test and the presence of hallux valgus, as well as the Silfverskiöld test and the presence of genu valgum with a p < .001. This study is the first to describe the association of gastrocnemius tightness, genu valgum and hallux valgus. Further studies are required to assess this relationship but knowledge and awareness of it can be applied by clinicians when considering the most appropriate management options with patients.
35300367 Validated DBS method for filgotinib quantitation in rat dried blood spots and its applicat 2020 Filgotinib is a selective JAK1 (Janus kinase) inhibitor, showed efficacy in patients suffering from moderate-to-severe rheumatoid arthritis. In this paper, we present the data on the development and validation of a sensitive, selective and high-throughput LC-MS/MS (liquid chromatography with tandem mass spectrometry) method for the quantitation of filgotinib from rat dried blood spot (DBS) cards. To the DBS disc cards, 0.2% formic acid enriched with internal standard (IS) was added and sonicated. Thereafter the extraction of filgotinib and the IS (tofacitinib) was accomplished using ethyl acetate as an extraction solvent. The resolution of filgotinib and the IS was achieved on a Gemini C(18) column with an isocratic mobile phase, which is a mixture of 0.2% formic acid:acetonitrile (20:80, v/v) at a flow-rate of 0.9 mL/min. The total run time was 2.90 min and the retention time of filgotinib and the IS was ~1.31 and 0.89 min, respectively. Filgotinib and the IS were analyzed using positive ion scan mode and parent-daughter mass to charge ion (m/z) transition of 426.3→291.3 and m/z 313.2→149.2, respectively, for quantitation. The calibration range was 1.37-1937 ng/mL. No matrix effect and carry over were observed. All the validation parameters met the acceptance criteria. The validated method has been applied to a pharmacokinetic study in rats. A good correlation between DBS and plasma concentrations for filgotinib was observed.
33224548 Case Series of Chronic Inflammatory Rheumatic Disease Patients Infected by Coronavirus Dis 2020 Coronavirus disease 2019 (COVID-19) is a viral infection that appeared in December 2019. The risk of infection seems to be increased in chronic inflammatory rheumatic diseases due to both immune disturbances related to the disease and treatment. In this case report, we describe the clinical features of 5 rheumatic immune disease patients with the concomitant presence of COVID-19. Among these patients, 3 had rheumatoid arthritis and 2 had systemic lupus erythematosus. Patients' age ranged between 38 and 63 years. Only one patient (SLE) had a severe subtype of COVID-19. All the patients were cured of COVID-19 and were subsequently discharged.
33205007 Current advances in regulation of bone homeostasis. 2020 Nov Bone homeostasis is securely controlled by the dynamic well-balanced actions among osteoclasts, osteoblasts and osteocytes. Osteoclasts are large multinucleated cells that degrade bone matrix and involve in the bone remodelling in conjunction with other bone cells, osteoblasts and osteocytes, the completely matured form of osteoblasts. Disruption of this controlling balance among these cells or any disparity in bone remodelling caused by a higher rate of resorption by osteoclasts over construction of bone by osteoblasts results in a reduction of bone matrix including bone mineral density (BMD) and bone marrow cells (BMCs). The dominating effect of osteoclasts results in advanced risk of bone crack and joint destruction in several diseases including osteoporosis and rheumatoid arthritis (RA). However, the boosted osteoblastic activity produces osteosclerotic phenotype and weakened its action primes to osteomalacia or rickets. On the other hand, senescent osteocytes predominately progress the senescence associated secretory phenotype (SASP) and may contribute to age related bone loss. Here, we discuss an advanced level work on newly identified cellular mechanisms controlling the remodelling of bone and crosstalk among bone cells as these relate to the therapeutic targeting of the skeleton.