Regulation and enzymatic basis of bone resorption by human osteoclasts

Fuller, K.; Kirstein, Barrie; Chambers, T.J.

doi:10.1042/cs20060274

Cited by 34 publications

(28 citation statements)

References 41 publications

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“…81,82 Both IL-6 and IL-8 are known to attract and activate osteoclasts and to play a role in prostate cancer. 49,53,83,84 Osteoclast formation by PC3-derived IL-6 and IL-8 was recently shown to be RANKL-independent. 53 Our results suggest a RANKL-dependent interaction between IL-8 and cathepsin K, but not between IL-6 and cathepsin K. Given the importance of cathepsin K for osteoclast differentiation and function, 55,56 further studies will be needed to validate the contribution of cathepsin K-mediated secretion of pro-inflammatory factors to osteolysis and progression of prostate tumors in the bone.…”

Section: Discussionmentioning

confidence: 99%

Bone Marrow-Derived Cathepsin K Cleaves SPARC in Bone Metastasis

Podgorski

Linebaugh

Koblinski

et al. 2009

The American Journal of Pathology

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Prostate and breast cancers commonly metastasize to skeletal sites and locally disrupt normal bone remodeling.Despite recent progress in cancer detection and treatment, it remains unclear which skeletal-specific factors are among the critical determinants in preferential localization of metastatic cells to the bone. Recent clinical and experimental data suggest that accelerated bone remodeling may be responsible for homing of tumor cells to the bone.1,2 This is evidenced by the increased metastasis in response to experimental treatment with calciotropic hormone or to androgen ablation 1,2 and reduced incidence of metastasis with antiresorptive therapies.3 Establishment of tumors in bone requires multidirectional interactions between tumor cells, bone cells, stromal cells, and inflammatory components, as well as extracellular matrix proteins. This complex interplay between tumor cells and the bone microenvironment facilitates increased bone turnover and promotes tumor cell survival.The key enzyme responsible for osteolysis of bone is the cysteine protease cathepsin K, which is the only known mammalian protease capable of degrading both the helical and non-helical regions of collagen I, the main component of the organic bone matrix. 4 Within the bone microenvironment, cathepsin K localizes predominantly to osteoclasts and its overexpression results in increased bone turnover.5 Accordingly, a deficiency in this potent collagenase results in a bone-sclerosing disorder called pycnodysostosis in man and osteopetrosis in mice. 6,7 The presence of cathepsin K has been demonstrated in many malignancies including prostate and breast cancers, both of which have a high propensity to metastasize to bone. 8 -10 A role for cathepsin K in advanced cancers has been attributed mainly to its ability to degrade native collagen I and facilitate the expansion of tumors in the bone. Our recent studies and data by other groups suggest that cathepsin K also cleaves and thereby modulates the biological activity of several important proteins in the bone microenvironment.11-15 Of particular importance is Supported by grants from the DOD PC030325. DOD PC074031. DOD

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Section: Discussionmentioning

confidence: 99%

Bone Marrow-Derived Cathepsin K Cleaves SPARC in Bone Metastasis

Podgorski

Linebaugh

Koblinski

et al. 2009

The American Journal of Pathology

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“…In the sealed resorption lacuna, localized acidification is driven by carbonic anhydrase II and vacuolar H(+)-ATPase in osteoclasts; carbonic anhydrase II produces protons and vacuolar H(+)-ATPase transfers them into the lacuna. In acidified lacuna, cathepsin-K and matrix metalloproteinase-9 (MMP-9) are released from osteoclasts to degrade calcified tissues [9]. …”

Section: Osteoclasts Are Formed From Monocytes Stimulated By Ranklmentioning

confidence: 99%

Effects of NSAIDs on Differentiation and Function of Human and Murine Osteoclasts – Crucial ‘Human Osteoclastology’

et al. 2010

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Osteoclasts play a critical role in both normal bone metabolism and bone resorption in the joints of patients with rheumatoid arthritis. It has been reported that non-steroidal anti-inflammatory drugs (NSAIDs) inhibit murine osteoclastogenesis in vitro and murine arthritis models in vivo, but not the destruction of joints of patients with rheumatoid arthritis. In the current review article, we review the recent findings in the effect of NSAIDs on the formation and function of human and murine osteoclasts both in vitro and in vivo, underlining the importance of studies using human osteoclasts. Since 2009, we have suggested a novel term ‘human osteoclastology’.

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“…Bone slices with purified mature osteoclasts were transferred to new wells and incubated for an additional 3 days with M-CSF, TNF-␣, and IL-1␣ with or without different concentrations of IL-3. The resorption activity in bone cell culture supernatants was determined by quantifying CTX-I by CrossLaps ELISA (29). We found that IL-3 had no effect on CTX-I in mature osteoclasts (data not shown).…”

Section: Effect Of Il-3 On Bone Resorption By Mature Osteoclasts and mentioning

confidence: 99%

“…a CrossLaps ELISA kit (29). One-step ELISA was performed according to the manufacturer's instructions (Nordic Bioscience Diagnostics).…”

Section: Crosslaps Elisamentioning

confidence: 99%

IL-3 Inhibits TNF-α-Induced Bone Resorption and Prevents Inflammatory Arthritis

Yogesha

Khapli

Srivastava

et al. 2009

The Journal of Immunology

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IL-3, a cytokine secreted by activated T cells is well known to regulate the proliferation, differentiation, and survival of pluripotent hematopoietic stem cells. IL-3 functions as a link between the immune and the hematopoietic system. In this study, we suggest an important new role of IL-3 in inhibition of TNF-α-induced bone resorption in vitro and prevention of inflammatory arthritis in mice. We show here that IL-3 potently and irreversibly inhibits TNF-α-induced bone resorption in hematopoietic precursors of monocyte/macrophage lineage. IL-3 showed an inhibitory effect on TNF-α-induced bone resorption even in the presence of proinflammatory cytokines such as IL-1α, TGF-β1, TGF-β3, IL-6, and PGE2. We found that IL-3 prevented TNF-α-induced c-fos nuclear translocation and AP-1 DNA-binding activity. Interestingly, IL-3 pretreatment prevented the development of inflammatory arthritis in mice induced by a mixture of anti-type II collagen mAbs and LPS. Furthermore, IL-3 prevented cartilage and bone loss in the joints indirectly through inhibition of inflammation. Thus, we provide the first evidence that IL-3, a strong regulator of hematopoiesis, also plays an important role in inhibition of TNF-α-induced bone resorption and prevention of inflammatory arthritis in mice.

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Regulation and enzymatic basis of bone resorption by human osteoclasts

Cited by 34 publications

References 41 publications

Bone Marrow-Derived Cathepsin K Cleaves SPARC in Bone Metastasis

Bone Marrow-Derived Cathepsin K Cleaves SPARC in Bone Metastasis

Effects of NSAIDs on Differentiation and Function of Human and Murine Osteoclasts – Crucial ‘Human Osteoclastology’

IL-3 Inhibits TNF-α-Induced Bone Resorption and Prevents Inflammatory Arthritis

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