Extracellular fluid flow and chloride content modulate H+ transport by osteoclasts

Morethson, Priscilla

doi:10.1186/s12860-015-0066-4

Cited by 8 publications

(8 citation statements)

References 42 publications

(33 reference statements)

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“…However, additional mechanisms have been implicated in the acidification of the resorption lacuna: osteoclast acidification occurs under continuous flow conditions and exhibits progressive intracellular acidification, accompanied by spontaneous rhythmic oscillations of intracellular pH. The regulation of intracellular pH is related to the translocation of several ions across the plasma membrane by specific proteins [44], like Cl − secretion by chloride channel 7 (ClC-7) [44, 45]. In this process, intracellular pH is also maintained by H + conductance and the activity of the NHE10 isoform [44, 46], or by the base-transporters NBCn1 (Na + -HCO3 − co-transporter) [47] (see Bødkjer, this volume), and AE2 (Cl − /HCO3 − anion exchanger) [48].…”

Section: The Formation Of Acid Tme In Bone Metastasismentioning

confidence: 99%

“…The regulation of intracellular pH is related to the translocation of several ions across the plasma membrane by specific proteins [44], like Cl − secretion by chloride channel 7 (ClC-7) [44, 45]. In this process, intracellular pH is also maintained by H + conductance and the activity of the NHE10 isoform [44, 46], or by the base-transporters NBCn1 (Na + -HCO3 − co-transporter) [47] (see Bødkjer, this volume), and AE2 (Cl − /HCO3 − anion exchanger) [48]. Notably, although NHE1 is involved in osteoclast formation and function, it is not involved in lacunae acidification [49, 50].…”

Section: The Formation Of Acid Tme In Bone Metastasismentioning

confidence: 99%

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Cause and effect of microenvironmental acidosis on bone metastases

Avnet

Pompo

Lemma

et al. 2019

Cancer Metastasis Rev

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Skeletal involvement is a frequent and troublesome complication in advanced cancers. In the process of tumor cells homing to the skeleton to form bone metastases (BM), different mechanisms allow tumor cells to interact with cells of the bone microenvironment and seed in the bone tissue. Among these, tumor acidosis has been directly associated with tumor invasion and aggressiveness in several types of cancer although it has been less explored in the context of BM. In bone, the association of local acidosis and cancer invasiveness is even more important for tumor expansion since the extracellular matrix is formed by both organic and hard inorganic matrices and bone cells are used to sense protons and adapt or react to a low pH to maintain tissue homeostasis. In the BM microenvironment, increased concentration of protons may derive not only from glycolytic tumor cells but also from tumor-induced osteoclasts, the bone-resorbing cells, and may influence the progression or symptoms of BM in many different ways, by directly enhancing cancer cell motility and aggressiveness, or by modulating the functions of bone cells versus a pro-tumorigenic phenotype, or by inducing bone pain. In this review, we will describe and discuss the cause of acidosis in BM, its role in BM microenvironment, and which are the final effectors that may be targeted to treat metastatic patients.

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Section: The Formation Of Acid Tme In Bone Metastasismentioning

confidence: 99%

Section: The Formation Of Acid Tme In Bone Metastasismentioning

confidence: 99%

Cause and effect of microenvironmental acidosis on bone metastases

Avnet

Pompo

Lemma

et al. 2019

Cancer Metastasis Rev

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“…25 Following the adhesion of OCs to the bone surface, activated OCs form the ruffled border (RB) within the sealed zone, and secrete the acidic ions such as H + and Cl − into the bone extracellular matrix (ECM) to establish the acidic milieu of resorption lacuna, and to dissolve the mineralized ECM. [26][27][28] Destruction of mineralized ECM causes the exposure of organic elements, which are subsequently degraded by several of secreted lysosomal enzymes such as TRAP, CTSK, and MMP9, thereby triggering bone resorption. [29][30][31] Importantly, it has been well-characterized that the secretory route of the lysosomal enzymes is supported by the Rab GTPase-mediated transport vesicles.…”

Section: Introductionmentioning

confidence: 99%

“…For OC‐induced bone resorption, OCs are required to adhere to the bone surface to create a sealing zone 25 . Following the adhesion of OCs to the bone surface, activated OCs form the ruffled border (RB) within the sealed zone, and secrete the acidic ions such as H + and Cl − into the bone extracellular matrix (ECM) to establish the acidic milieu of resorption lacuna, and to dissolve the mineralized ECM 26–28 . Destruction of mineralized ECM causes the exposure of organic elements, which are subsequently degraded by several of secreted lysosomal enzymes such as TRAP, CTSK, and MMP9, thereby triggering bone resorption 29–31 .…”

Section: Introductionmentioning

confidence: 99%

Rab34 plays a critical role as a bidirectional regulator of osteoclastogenesis

Feng

Tran

et al. 2022

Cell Biochemistry & Function

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Accumulating evidence suggests that Rab GTPases representing the largest branch of Ras superfamily have recently emerged as the core factors for the regulation of osteoclastogenesis through modulating vesicular transport amongst specific subcellular compartments. Among these, Rab34 GTPase has been identified to be important for the post-Golgi secretory pathway and for phagocytosis; nevertheless, its specific role in osteoclastogenesis has been completely obscure. Here, upon the in vitro model of osteoclast formation derived from murine macrophages like RAW-D cells or bone marrow-derived macrophages, we reveal that Rab34 regulates osteoclastogenesis bidirectionally. More specifically, Rab34 serves as a negative regulator of osteoclast differentiation by promoting the lysosome-induced proteolysis of two osteoclastogenic surface receptors, c-fms and RANK, via the axis of early endosomes-late endosomes-lysosomes, leading to alleviate the transcriptional activity of two of the master regulator of osteoclast differentiation, c-fos and NFATc-1, eventually attenuating osteoclast differentiation and bone resorption. Besides, Rab34 plays a crucial role in modulating the secretory network of lysosome-related proteases including matrix metalloprotease 9 and Cathepsin K across the ruffled borders of osteoclasts, contributing to the regulation of bone resorption.

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“…A mutation in CA II can cause osteopetrosis due to non-functional osteoclasts [45]. The HCO 3 ions are exchanged for Clthrough an anion exchanger, a membrane transporter protein AE2 located in the basolateral membrane, leading to continued influx of Clfor acidification of the resorption lacuna [96,97]. After solubilization of the mineral phase, several proteolytic enzymes degrade the organic bone matrix, although the detailed sequence of events at the resorption lacuna is still obscure.…”

mentioning

confidence: 99%

Vascular Calcification, Atherosclerosis and Bone Loss (Osteoporosis): New Pathophysiological Mechanisms and Future Perspectives for Pharmacological Therapy

2016

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Vascular calcification or ectopic mineralization in blood vessels is an active, cell-regulated process, increasingly recognized as a general cardiovascular risk factor. Ectopic artery mineralization is frequently accompanied by decreased bone mineral density or disturbed bone turnover and development of the osteoporosis. The latest data support the correlation of osteoporosis and atherosclerosis, indicating the parallel progression of two tissue destruction processes with increased fatal and nonfatal coronary events, as well as a higher fracture risk. Patients with osteoporosis, have a higher risk of cardiovascular diseases than subjects with normal bone. Many proteins responsible for bone formation and resorption have been identified in the arterial wall. Vascular calcification includes mostly osteogenic and, to a lesser extent chondrogenic differentiation of osteoblasts and osteoclast-like cells. It has been shown that many of the regulators of bone formation and resorption some bone structural proteins, such as osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL) are also expressed in the atherosclerotic plaque. When RANKL binds to RANK, osteoclasts are activated and bone resorption occurs and processes of vascular calcification become also activated. OPG, protein homologue to receptor activator of nuclear factor-κB (RANK), can bind to RANKL, blocking the binding of RANKL to RANK, that results in inhibition of differentiation of preosteoclasts to mature osteoclasts, lower osteoclast capacity for resorption of bone mineral matrix, and development vascular calcification. The latest data supports that cathepsin K, a cysteine protease, can efficiently degrade type I and II collagen, both of which are major matrix components of the bone and atherosclerotic plaque. These findings further underscore the potential of cathepsin K as a target for novel molecules to treat osteoporosis and atherosclerosis. Thus, the discovery of the cytokine RANKL-RANK-OPG system and significant role of the cathepsin K in the process of bone remodeling, vascular calcification and atherosclerosis has made progress in understanding the mechanisms of disease development and possibly to develop new dual therapies. New therapies for osteoporosis and atherosclerosis that may potentially improve or augment existing treatments include the recently approved anti-receptor activator of NF-κB-ligand monoclonal antibody fms (denosumab) and the cathepsin K inhibitor odanacatib, presently in the late stage of clinical development.

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Extracellular fluid flow and chloride content modulate H+ transport by osteoclasts

Cited by 8 publications

References 42 publications

Cause and effect of microenvironmental acidosis on bone metastases

Cause and effect of microenvironmental acidosis on bone metastases

Rab34 plays a critical role as a bidirectional regulator of osteoclastogenesis

Vascular Calcification, Atherosclerosis and Bone Loss (Osteoporosis): New Pathophysiological Mechanisms and Future Perspectives for Pharmacological Therapy

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