Involvement of acidic microenvironment in the pathophysiology of cancer-associated bone pain

Yoneda, Toshiyuki; Hata, Kenji; Nakanishi, Masayoshi; Nagae, Maho; Nagayama, Tomotaka; Wakabayashi, Hiroki; Nishisho, Toshihiko; Sakurai, Teruhisa; Hiraga, Toru

doi:10.1016/j.bone.2010.07.009

Cited by 94 publications

(65 citation statements)

References 55 publications

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“…However, other potential mechanisms may be involved. For example, the acidic environment created by osteoclasts could cause bone pain during subchondral bone remodeling [19,39] . Nevertheless, weight-bearing asymmetry and CGRP expression were similar in MMT/NS rats and MMT/ZOL8 rats.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of zoledronic acid in treatment of teoarthritis is dependent on the disease progression stage in rat medial meniscal tear model

Mao

et al. 2012

Acta Pharmacol Sin

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Aim: To investigate whether the stage of osteoarthritis (OA) progression influenced the efficacy of the third-generation bisphosphonate zoledronic acid in a rat medial meniscal tear model. Methods: Medial meniscal tear (MMT) was surgically induced in adult male Sprague Dawley rats. Zoledronic acid (ZOL, 100 μg/kg, sc, twice a week) was administered starting immediately, early (from 4 weeks) or late (from 8 weeks) after OA induction. The degeneration of articular cartilage was evaluated with toluidine blue O staining. Subchondral bone remodeling was evaluated with X-ray micro-CT scanning. Joint pain was measured with respect to weight-bearing asymmetry. Calcitonin gene-related peptide (CGRP) expression in dorsal root ganglia (DRGs) was examined using immunofluorescence analysis. The afferent neurons in DRGs innervating the joint were identified by retrograde labeling with fluorogold. Results: Progressive cartilage loss was observed during 12 weeks after OA induction. Subchondral bone remodeling manifested as increased bone resorption at early stage (4 weeks), but as increased bone accretion at advanced stages (8 weeks). Immediately and early ZOL administration significantly improved subchondral microstructural parameters, attenuated cartilage degeneration, reduced weight-bearing asymmetry and CGRP expression, whereas the late ZOL administration had no significant effects. Conclusion: The stage of OA progression influences the efficacy of ZOL in treating joint degeneration and pain. To obtain the maximum efficacy, bisphosphonate treatment should be initiated in rat with early stages of OA pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Efficacy of zoledronic acid in treatment of teoarthritis is dependent on the disease progression stage in rat medial meniscal tear model

Mao

et al. 2012

Acta Pharmacol Sin

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“…Studies have highlighted that heightened osteoclast activity can lead to acidosis and the resultant protons can stimulate nociceptors on the surface of sensory neurons [126]. Recently, new data has also revealed the importance of neuronal factors and the sympathetic nervous system in controlling bone homeostasis and cancer progression in the bone microenvironment.…”

Section: Innervation Of the Vicious Cyclementioning

confidence: 99%

Integrating new discoveries into the “vicious cycle” paradigm of prostate to bone metastases

Cook

Shay

Aruajo

et al. 2014

Cancer Metastasis Rev

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Summary In prostate to bone metastases, the “vicious cycle” paradigm has been traditionally used to illustrate how metastases manipulate the bone forming osteoblasts and resorbing osteoclasts in order to yield factors that facilitate the growth and establishment. However, recent advances have illustrated that the cycle is far more complex than this simple interpretation. In this review, we will discuss the role of exosomes and hematopoietic/mesenchymal stem cells facilitate the establishment and activation of prostate metastases and, how cells including such as myeloid derived suppressor cells, macrophages, T-cells and nerve cells contribute to the momentum of the vicious cycle. The increased complexity of the tumor-bone microenvironment requires a systems level approach. The evolution of computational models to interrogate the tumor-bone microenvironment is also discussed and the application of this integrated approach should allow for the development of effective therapies to treat and cure prostate to bone metastases.

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“…In the case of rutin-loaded microspheres, the release rate was evaluated in two different relevant physiological conditions, that is, at a physiological pH and at a pH of 5 ( Figure 2); in fact, it is well-known that the environment of a flogistic area is characterized by an acid pH (Yoneda et al, 2011;Aoki, Mogi & Okajima, 2014). The release profiles of the drug at the two different pH conditions was similar, even though pH 5 allowed a greater amount of rutin leakage from the chitosan matrix, probably as a consequence of the protonation of the aminic residues, which induces a destabilization of the biopolymeric network of microspheres.…”

Section: Characterization Of Chitosan Microspheresmentioning

confidence: 99%

Rutin-loaded chitosan microspheres: Characterization and evaluation of the anti-inflammatory activity

Cosco

Failla

Costa

et al. 2016

Carbohydrate Polymers

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Involvement of acidic microenvironment in the pathophysiology of cancer-associated bone pain

Cited by 94 publications

References 55 publications

Efficacy of zoledronic acid in treatment of teoarthritis is dependent on the disease progression stage in rat medial meniscal tear model

Efficacy of zoledronic acid in treatment of teoarthritis is dependent on the disease progression stage in rat medial meniscal tear model

Integrating new discoveries into the “vicious cycle” paradigm of prostate to bone metastases

Rutin-loaded chitosan microspheres: Characterization and evaluation of the anti-inflammatory activity

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