The Roles of Acidosis in Osteoclast Biology

Yuan, Feng-Lai; Xu, Minghui; Li, Xia; He, Xiuping; Fang, Wei; Dong, Jian

doi:10.3389/fphys.2016.00222

Cited by 57 publications

(47 citation statements)

References 103 publications

(137 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…OGR1 does not desensitize and is the only proton-sensing GPCR coupling to changes in [Ca 2+ ] i [14,27], which determine a plethora of physiological as well as underlie pathological processes. OGR1 affects a number of distinct cellular processes and, in light of our findings, its role in enamel formation [28] and bone development [29][30][31] is particularly intriguing: enamel and bone are the hardest materials in the human body, and enamel formation and bone development both require cycles of extracellular acidification [32,33].…”

Section: Discussionmentioning

confidence: 71%

See 1 more Smart Citation

Coincidence Detection of Membrane Stretch and Extracellular pH by the Proton-Sensing Receptor OGR1 (GPR68)

et al. 2018

View full text Add to dashboard Cite

Highlights d OGR1 (aka GPR68) requires cell stretch and extracellular protons to activate d Cell stretch and extracellular acidosis synergistically promote OGR1 signaling d Cell-stretch-mediated actin polymerization is crucial for OGR1 activity d Actin depolymerization limits how long OGR1 stays responsive after cell stretch SUMMARYThe physical environment critically affects cell shape, proliferation, differentiation, and survival by exerting mechanical forces on cells. These forces are sensed and transduced into intracellular signals and responses by cells. A number of different membrane and cytoplasmic proteins have been implicated in sensing mechanical forces, but the picture is far from complete, and the exact transduction pathways remain largely elusive. Furthermore, mechanosensation takes place alongside chemosensation, and cells need to integrate physical and chemical signals to respond appropriately and ensure normal tissue and organ development and function. Here, we report that ovarian cancer G protein coupled receptor 1 (OGR1) (aka GPR68) acts as coincidence detector of membrane stretch and its physiological ligand, extracellular H + . Using fluorescence imaging, substrates of different stiffness, microcontact printing methods, and cell-stretching techniques, we show that OGR1 only responds to extracellular acidification under conditions of membrane stretch and vice versa. The level of OGR1 activity mirrors the extent of membrane stretch and degree of extracellular acidification. Furthermore, actin polymerization in response to membrane stretch is critical for OGR1 activity, and its depolymerization limits how long OGR1 remains responsive following a stretch event, thus providing a ''memory'' for past stretch. Cells experience changes in membrane stretch and extracellular pH throughout their lifetime. Because OGR1 is a widely expressed receptor, it represents a unique yet widespread mechanism that enables cells to respond dynamically to mechanical and pH changes in their microenvironment by integrating these chemical and physical stimuli at the receptor level. Current Biology 28, 3815-3823, December 3, 2018 ª 2018 Elsevier Ltd. 3815 FIJI NIH https://fiji.sc/ Driver software for custom built stretch machine Zaber Console https://www.zaber.com/zaber-software e1 Current Biology 28, 3815-3823.e1-e4, December 3, 2018

show abstract

Section: Discussionmentioning

confidence: 71%

“…Extracellular acidification and increases in tissue stiffness are also associated with aging [33,34] and accompany and promote disease progression [35][36][37]. This places OGR1 in an exceptional position, as it is synergistically activated by both and hence sensitive to even small changes.…”

Section: Discussionmentioning

confidence: 99%

Coincidence Detection of Membrane Stretch and Extracellular pH by the Proton-Sensing Receptor OGR1 (GPR68)

et al. 2018

View full text Add to dashboard Cite

show abstract

“…The formation of osteoclasts in culture was also found to be a dominant end effect of acidosis, as Trap5b expression was similar in both top and bottom sections of ch‐ch constructs and the differences in pO 2 was negligible. Also shown in other literatures, acidosis was reported to enhance osteoclast formation in cats (Muzylak, Arnett, Price, & Horton, ) and regulates survival of mature rat osteoclast (Pereverzev et al, ; Yuan et al, ). Additionally, the elevated expression of sclerostin ( Sost ) would have also induced Trap5b expression via the RANKL‐dependent pathway for bone remodelling and resorption (Weivoda, Youssef, & Oursler, ; Wijenayaka et al, ).…”

Section: Discussionmentioning

confidence: 60%

“…Also shown in other literatures, acidosis was reported to enhance osteoclast formation in cats (Muzylak, Arnett, Price, & Horton, 2007) and regulates survival of mature rat osteoclast (Pereverzev et al, 2008;Yuan et al, 2016). Additionally, the elevated expression of sclerostin (Sost) would have also induced Trap5b expression via the RANKL-dependent pathway for bone remodelling and resorption (Weivoda, Youssef, & Oursler, 2017;Wijenayaka et al, 2011).…”

Section: Discussionmentioning

confidence: 73%

Recapitulating bone development events in a customised bioreactor through interplay of oxygen tension, medium pH, and systematic differentiation approaches

Lee

Hess

Friedrichs

et al. 2019

J Tissue Eng Regen Med

View full text Add to dashboard Cite

Bone development and homeostasis are intricate processes that require co‐existence and dynamic interactions among multiple cell types. However, controlled dynamic niches that derive and support stable propagation of these cells from single stem cell source is not sustainable in conventional culturing vessels. In bioreactor cultures that support dynamic niches, the limited source and stability of growth factors are often a major limiting factor for long‐term in vitro cultures. Hence, alternative growth factor‐free differentiation approaches are designed and their efficacy to achieve different osteochondral cell types is investigated. Briefly, a dynamic niche is achieved by varying medium pH, oxygen tension (pO2) distribution in bioreactor, initiating chondrogenic differentiation with chondroitin sulphate A (CSA), and implementing systematic differentiation regimes. In this study, we demonstrated that CSA is a potent chondrogenic inducer, specifically in combination with acidic medium and low pO2. Further, endochondral ossification is recapitulated through a systematic chondrogenic–osteogenic (ch‐os) differentiation regime, and multiple osteochondral cell types are derived. Chondrogenic hypertrophy was also enhanced specifically in high pO2 regions. Consequently, mineralised constructs with higher structural integrity, volume, and tailored dimensions are achieved. In contrast, a continuous osteogenic differentiation regime (os‐os) has derived compact and dense constructs, whereas a continuous chondrogenic differentiation regime (ch‐ch) has attenuated construct mineralisation and impaired development. In conclusion, a growth factor‐free differentiation approach is achieved through interplay of pO2, medium pH, and systematic differentiation regimes. The controlled dynamic niches have recapitulated endochondral ossification and can potentially be exploited to derive larger bone constructs with near physiological properties.

show abstract

“…In people with osteoporosis, bone loss is due to increased osteoclast activity, and decreased osteoblastic bone formation cannot keep pace with bone resorption ( 4 , 5 ). Most existing therapeutics for osteoporosis are antiresorptive drugs, such as bisphosphonates, and anabolic medications, including denosumab and teriparatide ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

Long Non-coding RNAs: A New Regulatory Code for Osteoporosis

Miao

et al. 2018

Front. Endocrinol.

Self Cite

View full text Add to dashboard Cite

Osteoporosis is a metabolic bone disease characterized by a decrease in bone mass and degradation of the bone microstructure, which increases bone fragility and fracture risk. However, the molecular mechanisms of osteoporosis remain unclear. Long non-coding RNAs (lncRNAs) have become important epigenetic regulators controlling the expression of genes and affecting multiple biological processes. Accumulating evidence of the involvement of lncRNAs in bone remolding has increased understanding of the molecular mechanisms underlying osteoporosis. This review aims to summarize recent progress in the elucidation of the role of lncRNAs in bone remodeling, and how it contributes to osteoblast and osteoclast function. This knowledge will facilitate the understanding of lncRNA roles in bone biology and shed new light on the modulation and potential treatment of osteoporosis.

show abstract

The Roles of Acidosis in Osteoclast Biology

Cited by 57 publications

References 103 publications

Coincidence Detection of Membrane Stretch and Extracellular pH by the Proton-Sensing Receptor OGR1 (GPR68)

Coincidence Detection of Membrane Stretch and Extracellular pH by the Proton-Sensing Receptor OGR1 (GPR68)

Recapitulating bone development events in a customised bioreactor through interplay of oxygen tension, medium pH, and systematic differentiation approaches

Long Non-coding RNAs: A New Regulatory Code for Osteoporosis

Contact Info

Product

Resources

About