Disesase Main Main biochemical Main cause feateures changes
Cyrus Cooper, John Harrison, Roger Smith in Shared Care For Osteoporosis, 1999
Major determinants The main determinants of bone mass are those that influence the balance between osteoblast and osteoclast activity-namely, the interaction between genetic and mechanical factors, modified by nutritional and endocrine influences. These have been considered previously and some examples are shown in Figure 2.12. Recent research has failed to establish any single clear cause of the difference between the bone mass of adult Whites and Blacks and of Caucasians and Orientals. The combined effect of malnutrition and oestrogen deficiency in anorexia nervosa has received much attention. Likewise, obsessional exercise associated with oestrogen lack is a recognised cause of low bone mass in females, whereas in those who are not hormone deficient the beneficial effect of mechanical stress on the skeleton continues to be confirmed.
Mechanical Stress and Bone Remodeling
Wilson Harvey, Alan Bennett in Prostaglandins in Bone Resorption, 2020
Since the end of the last century when J. Wolff postulated that bone remodels in such a way that it attains maximum resistance to applied forces, a large body of evidence has established the link between mechanical loading and elevated rates of remodeling. The basis of orthodontic tooth movement is simple, that teeth move through bone in a response to an applied mechanical force. This involves bone remodeling. Although the resistance of cementum to resorption is not directly relevant to prostaglandins (PGs), it is an intriguing phenomenon, and like the normal resistance of cartilage to vascularization and osteoclastic resorption, it could tells a lot about the regulation of resorption. The involvement of PGs in orthodontic tooth movement was first suggested by Z. Davidovitch and J. L. Shanfeld as a possible explanation of the changes in cyclic nucleotides they had observed.
What are the problems of bone cell biology?
Cyrus Cooper, John Harrison, Roger Smith in Shared Care For Osteoporosis, 1999
These are innumerable2. We have some idea of where bone cells come from and what they do (Chapter 2), but we have very little idea of how they ‘talk’ to each other. Legions of putative cellular messengers (cytokines) are described, but nearly all research is conducted in vitro on cells of dubious derivation and little applies in vivo to the human skeleton. Despite this-and since we must start somewhere-it remains important to unravel the nature of the linkage between the osteoblast and osteoclast, as these so-called ‘coupling factors’ are likely to be central to skeletal biology.
Dasatinib inhibits both osteoclast activation and prostate cancer PC-3 cell-induced osteoclast formation
Published in Cancer Biology & Therapy, 2009
John C. Araujo, Ann Poblenz, Nila U. Parikh, Michael W. Starbuck, Jerry T. Thompson, Francis Lee, Christopher J. Logothetis, Bryant G. Darnay
Purpose: Therapies to target prostate cancer bone metastases have only limited effects. New treatments are focused on the interaction between cancer cells, bone marrow cells and the bone matrix. Osteoclasts play an important role in the development of bone tumors caused by prostate cancer. Since Src kinase has been shown to be necessary for osteoclast function, we hypothesized that dasatinib, a Src family kinase inhibitor, would reduce osteoclast activity and prostate cancer (PC-3) cell-induced osteoclast formation. Experimental Design: We performed in vitro experiments utilizing the Src family kinase inhibitor dasatinib to target osteoclast activation as a means of inhibiting prostate cancer bone metastases. Results: Dasatinib inhibited RANKL-induced osteoclast differentiation of bone marrow-derived monocytes with an EC50 of 7.5 nM. PC-3 cells, a human prostate cancer cell line, were able to differentiate RAW 264.7 cells, a murine monocytic cell line, into osteoclasts, and dasatinib inhibited this differentiation. In addition, conditioned medium from PC-3 cell cultures was able to differentiate RAW 264.7 cells into osteoclasts and this too, was inhibited by dasatinib. Even the lowest concentration of dasatinib, 1.25 nmol, inhibited osteoclast differentiation by 29%. Moreover, dasatinib inhibited osteoclast activity by 58% as measured by collagen 1 release. Conclusion: Dasatinib inhibits osteoclast differentiation of mouse primary bone marrow-derived monocytes and PC-3 cell-induced osteoclast differentiation. Dasatinib also inhibits osteoclast degradation activity. Inhibiting osteoclast differentiation and activity may be an effective targeted therapy in patients with prostate cancer bone metastases.
Nitric oxide modulates the responses of osteoclast formation to static magnetic fields
Published in Electromagnetic Biology and Medicine, 2018
Jian Zhang, Chong Ding, Xiaofeng Meng, Peng Shang
ABSTRACT Nitric oxide (NO) is involved in osteoclast differentiation. Our previous studies showed that static magnetic fields (SMFs) could affect osteoclast differentiation. The inhibitory effects of 16 T of high SMF (HiMF) on osteoclast differentiation was correlated with increased production of NO. We raised the hypothesis that NO mediated the regulatory role of SMFs on osteoclast formation. In this study, 500 nT of hypomagnetic field (HyMF), 0.2 T of moderate SMF (MMF) and 16 T of high SMF (HiMF) were utilized as SMF treatment. Under 16 T, osteoclast formation was markedly decreased with enhanced NO synthase (NOS) activity, thus producing a high level of NO. When treated with NOS inhibitor N-Nitro-L-Arginine Methyl Ester (L-NAME), NO production could be inhibited, and osteoclast formation was restored to control group level in a concentration-dependent manner. However, 500 nT and 0.2 T increased osteoclast formation with decreased NOS activity and NO production. When treated with NOS substrate L-Arginine (L-Arg) or NO donor sodium nitroprusside (SNP), the NO level in the culture medium was obviously elevated, thus inhibiting osteoclast differentiation in a concentration-dependent manner under 500 nT or 0.2 T. Therefore, these findings indicate that NO mediates the regulatory role of SMF on osteoclast formation.
Osteoclastic resorptive capacity is suppressed in patients receiving hyperbaric oxygen therapy
Published in Acta Orthopaedica, 2015
Hadil Al Hadi, Gary Smerdon, Simon W Fox
Background and purpose — Hypoxia, necrosis, and bone loss are hallmarks of many skeletal diseases. Hyperbaric oxygen therapy (HBO) is often used as an adjunctive therapy in these cases. However the in vivo effect of HBO on osteoclast formation has not been fully established. We therefore carried out a longitudinal study to examine the effect of HBO on osteoclast formation and bone resorptive capacity in patients who were referred to the Plymouth Hyperbaric Medical Centre. Methods — Osteoclast precursors were isolated from peripheral blood prior to and following 10 and 25 daily hyperbaric treatments (100% O2 at 2.4 atmospheres absolute ATA for 90 min) to determine osteoclast formation and resorptive capacity. The expression of key regulators of osteoclast differentiation RANK, Dc-STAMP, and NFATc1 was also assessed by quantitative real-time PCR. Results — HBO reduced the ability of precursors to form osteoclasts and reduced bone resorption in a treatment-dependent manner. The initial suppressive effect of HBO was more pronounced on mononuclear osteoclast formation than on multinuclear osteoclast formation, and this was accompanied by reduction in the expression of key regulators of osteoclast formation, RANK and Dc-STAMP. Interpretation — This study shows for the first time that in vivo, HBO suppresses the ability of monocytic precursors to form resorptive osteoclasts.
Related Knowledge Centers
- Cementum
- Macrophage
- Monocyte
- Histiocyte
- Bone Resorption
- Epithelioid Cell