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April 12th

Modeling the interactions between osteoblast and osteoclast activities in bone remodeling ? CellML: In the paper described here, Lemaine et al. present a mathematical model of the interactions which occur between osteoblasts and osteoclasts in the process of bone remodelling. Using this model the authors were able to simulate skeletal disease by inserting dysfunctional connections in the coupling network to explore different disease hypotheses.
ScienceDirect - Journal of Theoretical Biology : Modeling the interactions between osteoblast and osteoclast activities in bone remodeling: The model results corroborate all behaviors of the bone remodeling system that we have simulated, including the tight coupling between osteoblasts and osteoclasts, the catabolic effect induced by continuous administration of PTH, the catabolic action of RANKL, as well as its reversal by soluble antagonist OPG. The model is also able to simulate metabolic bone diseases such as estrogen deficiency, vitamin D deficiency, senescence and glucocorticoid excess. Conversely, possible routes for therapeutic interventions are tested and evaluated. Our model confirms that anti-resorptiv e therapies are unable to partially restore bone loss, whereas bone formation therapies yield better results.

April 11th

Clinical applications of RANK-ligand inhibition. [Intern Med J. 2009] - PubMed Result: The effects of RANKL inhibition are being witnessed in clinical trials of neutralizing fully human monoclonal antibodies that target RANKL (e.g. denosumab) and which induce profound and sustained inhibition of bone resorption. The relative efficacy, cost-effective ness and side-effects of targeted RANKL inhibition compared with conventional antiresorptive drugs (i.e. bisphosphonate s) should be resolved by clinical trials in coming years.

April 10th

IL-17 in synovial fluids from patients with rheuma...[J Clin Invest. 1999] - PubMed Result: Osteoclastogen esis inhibitory factor (OCIF), a decoy receptor of ODF, completely inhibited IL-17-induced osteoclast differentiatio n in the cocultures. Levels of IL-17 in synovial fluids were significantly higher in rheumatoid arthritis (RA) patients than osteoarthritis (OA) patients. Anti-IL-17 antibody significantly inhibited osteoclast formation induced by culture media of RA synovial tissues. These findings suggest that IL-17 first acts on osteoblasts, which stimulates both COX-2-dependen t PGE2 synthesis and ODF gene expression, which in turn induce differentiatio n of osteoclast progenitors into mature osteoclasts, and that IL-17 is a crucial cytokine for osteoclastic bone resorption in RA patients.
Differential modulation of RANKL isoforms by human...[Bone. 2008] - PubMed Result: CONCLUSION: Our findings showed that the normal, L- and H-OA subchondral bone osteoblasts differentially express membranous RANKL and RANKL isoforms, and that treatment with osteotropic factors generally favours increased membranous localization of RANKL on L-OA compared to H-OA osteoblasts. This phenomenon appears to take place through differential modulation of each RANKL isoform.
Differential modulation of RANKL isoforms by human...[Bone. 2008] - PubMed Result: CONCLUSION: Our findings showed that the normal, L- and H-OA subchondral bone osteoblasts differentially express membranous RANKL and RANKL isoforms, and that treatment with osteotropic factors generally favours increased membranous localization of RANKL on L-OA compared to H-OA osteoblasts. This phenomenon appears to take place through differential modulation of each RANKL isoform.
The differential expression of osteoprotegeri n (OP...[Clin Exp Rheumatol. 2008 Mar-Apr] - PubMed Result

March 28th

Osteoprotegeri n administration reduces femural bon...[J Electron Microsc (Tokyo). 2002] - PubMed Result: Ultrastructura lly, OPG administration caused disappearance of ruffled borders in most osteoclasts, but induced neither necrotic nor apoptotic changes. In addition, the expression of vacuolar-type H+-ATPase in osteoclasts was decreased by OPG administration . Our results suggest that low-dose OPG administration significantly reduces trabecular bone loss in OVX mice via impairment of the structure and bone resorbing activity of osteoclasts.
Effects of chemically modified tetracycline, CMT-8...[Ann N Y Acad Sci. 1999] - PubMed Result: Our results suggest that CMT-8 therapy effectively inhibits post-ovariecto my bone loss not only by inducing new bone formation, but also by inhibiting osteoclastic bone resorption, and that CMT-8 binding to bone may provide a prolonged release delivery of this anti-resorptiv e therapy.
Effects of chemically modified tetracycline, CMT-8...[Ann N Y Acad Sci. 1999] - PubMed Result: Our results suggest that CMT-8 therapy effectively inhibits post-ovariecto my bone loss not only by inducing new bone formation, but also by inhibiting osteoclastic bone resorption, and that CMT-8 binding to bone may provide a prolonged release delivery of this anti-resorptiv e therapy.
IFN-gamma stimulates osteoclast formation and bone...[J Clin Invest. 2007] - PubMed Result: T cell-produced cytokines play a pivotal role in the bone loss caused by inflammation, infection, and estrogen deficiency. IFN-gamma is a major product of activated T helper cells that can function as a pro- or antiresorptive cytokine, but the reason why IFN-gamma has variable effects in bone is unknown.
Tumor necrosis factor-alpha: alternative role as a...[Bone. 2006] - PubMed Result: Dexamethasone blocked the secretion of the TNFalpha-depen dent inhibitor by osteoblasts, while stimulating the development of osteoclasts. The data suggest that the effects of TNFalpha on the differentiatio n of osteoclast lineage cells and on bone metabolism may be more complex than hitherto assumed and that these effects may play a role in vivo during therapies for inflammatory diseases.
Induction of osteoclast-lik e cells derived from th...[Osteoart hritis Cartilage. 2007] - PubMed Result: CONCLUSION: The results suggest that the joint-infiltra ting SF cells from TMD patients play important roles in the pathogenesis of these disorders, which is characterized by progressive bone destruction or remodeling.

March 22nd

Osteoprotegeri n reduces osteoclast numbers and pre...[Am J Pathol. 2002] - PubMed Result: These data demonstrate that short term Fc-OPG treatment has powerful anti-erosive effects, principally on bone, even though synovitis is not affected. These findings indicate the potential utility of disrupting RANK signaling to preserve skeletal integrity in inflammatory arthritis.

September 2nd