Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption

McDonald, Michelle M.; Khoo, Weng Hua; Ng, Pei Ying; Ye, Xiao; Zamerli, Jad; Thatcher, Peter; Kyaw, Wunna; Pathmanandavel, Karrnan; Grootveld, Abigail K.; Moran, Imogen; Butt, Danyal; Nguyen, Akira; Corr, Alexander; Warren, Sean; Biro, Maté; Butterfield, Natalie C.; Guilfoyle, Siobhan E.; Komla‐Ebri, Davide; Dack, Michael R.G.; Dewhurst, Hannah; Logan, John G.; Li, Yongxiao; Mohanty, Sindhu T.; Byrne, Niall; Terry, Rachael; Simic, Marija K.; Chai, Ryan C.; Quinn, Julian M.W.; Youlten, Scott E.; Pettitt, Jessica A.; Abi–Hanna, David; Jain, Rohit; Weninger, Wolfgang; Lundberg, Mischa; Sun, Shuting; Ebetino, Frank H.; Timpson, Paul; Lee, Woei Ming; Baldock, Paul A.; Rogers, Michael J.; Brink, Robert; Williams, Graham R.; Bassett, J. H. Duncan; Kemp, John P.; Pavlos, Nathan J.; Croucher, Peter I.; Phan, Tri Giang

doi:10.1016/j.cell.2021.03.010

Cited by 66 publications

(50 citation statements)

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“…In bone remodeling, osteoclasts are recruited to sites of microfractures, creating an acidic environment to dissolve minerals, and secrete digestive enzymes (cathepsins and collagenases) to remove the old bone. The fate of osteoclasts was unclear until recently, when cell-tracing and real-time imaging showed osteoclasts are recycled through fission to a distinct cell type termed “osteomorphs” [ 183 ]. Osteomorphs have a distinct molecular signature from marcophages and osteoclasts and are able to fuse again to form activated osteoclasts [ 183 ] ( Figure 1 D).…”

Section: Environmental Cues Regulating Osteogenesismentioning

confidence: 99%

“…The fate of osteoclasts was unclear until recently, when cell-tracing and real-time imaging showed osteoclasts are recycled through fission to a distinct cell type termed “osteomorphs” [ 183 ]. Osteomorphs have a distinct molecular signature from marcophages and osteoclasts and are able to fuse again to form activated osteoclasts [ 183 ] ( Figure 1 D). As old bone tissue is removed, osteoblasts are mobilized to rebuild the site, depositing new bone matrix enriched in collagen type I.…”

Section: Environmental Cues Regulating Osteogenesismentioning

confidence: 99%

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Regulation and Role of Transcription Factors in Osteogenesis

Chan

Tan

et al. 2021

IJMS

123

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Bone is a dynamic tissue constantly responding to environmental changes such as nutritional and mechanical stress. Bone homeostasis in adult life is maintained through bone remodeling, a controlled and balanced process between bone-resorbing osteoclasts and bone-forming osteoblasts. Osteoblasts secrete matrix, with some being buried within the newly formed bone, and differentiate to osteocytes. During embryogenesis, bones are formed through intramembraneous or endochondral ossification. The former involves a direct differentiation of mesenchymal progenitor to osteoblasts, and the latter is through a cartilage template that is subsequently converted to bone. Advances in lineage tracing, cell sorting, and single-cell transcriptome studies have enabled new discoveries of gene regulation, and new populations of skeletal stem cells in multiple niches, including the cartilage growth plate, chondro-osseous junction, bone, and bone marrow, in embryonic development and postnatal life. Osteoblast differentiation is regulated by a master transcription factor RUNX2 and other factors such as OSX/SP7 and ATF4. Developmental and environmental cues affect the transcriptional activities of osteoblasts from lineage commitment to differentiation at multiple levels, fine-tuned with the involvement of co-factors, microRNAs, epigenetics, systemic factors, circadian rhythm, and the microenvironments. In this review, we will discuss these topics in relation to transcriptional controls in osteogenesis.

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Section: Environmental Cues Regulating Osteogenesismentioning

confidence: 99%

Section: Environmental Cues Regulating Osteogenesismentioning

confidence: 99%

Regulation and Role of Transcription Factors in Osteogenesis

Chan

Tan

et al. 2021

IJMS

123

View full text Add to dashboard Cite

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“…These include the fact that these cells are of a stellate structure and form a syncytium on the bone surface (17,55), allowing us to revisit interpretations from serial 2D static sections made many decades ago (69).…”

Section: Accepted Articlementioning

confidence: 99%

New Insights Into Osteoclast Biology

et al. 2021

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“…Osteoclasts are derived from monocyte progenitor cells of haematopoietic origin and are the exclusive bone‐resorbing cells; their excessive activation is the prime culprit behind bone destruction [9,10]. Bone resorption involves decalcification and protein degradation process that are mediated by protein‐ and matrix‐degrading enzymes, such as cathepsin K and matrix metalloproteinases (MMPs), which are sourced from osteoclasts.…”

Section: Introductionmentioning

confidence: 99%

Dual effect of IL‐7/IL‐7R signalling on the osteoimmunological system: a potential therapeutic target for rheumatoid arthritis

Cai

et al. 2021

Immunology

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The IL‐7/IL‐7R pathway plays a vital role in the immune system, especially in the inflammatory response. Monocytes/macrophages (osteoclast precursors) have been recently recognized as important participants in the osteoclastogenesis of rheumatoid arthritis (RA) patients. Here, we aimed to investigate the therapeutic potential of IL‐7/IL‐7R pathway in RA and to determine whether it could restrain osteoclastogenic functions and therefore ameliorate RA. Firstly, collagen‐induced arthritis (CIA) mice were administered with IL‐7Rα‐target antibodies to assess their therapeutic effect on arthritis. We found that blockade of the IL‐7/IL‐7R pathway protected CIA mice from bone destruction in addition to inducing inflammatory remission, by altering the RANKL/RANK/OPG ratio and consequently decreasing osteoclast formation. To explore the effect and mechanism of this pathway, bone marrow cells were induced to osteoclasts and treated with IL‐7, a STAT5 inhibitor or supernatants from T cells. The results showed that the IL‐7/IL‐7R pathway played a direct inhibitory role in osteoclast differentiation via STAT5 signalling pathway in a RANKL‐induced manner. We applied flow cytometry to analyse the effect of IL‐7 on T‐cell RANKL expression and found that IL‐7/IL‐7R pathway had an indirect role in the osteoclast differentiation process by enhancing the RANKL expression on T cells. In conclusion, the IL‐7/IL‐7R pathway exhibited a dual effect on osteoclastogenesis of CIA mice by interacting with osteoimmunology processes and could be a novel therapeutic target for autoimmune diseases such as RA.

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Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption

Cited by 66 publications

References 0 publications

Regulation and Role of Transcription Factors in Osteogenesis

Regulation and Role of Transcription Factors in Osteogenesis

New Insights Into Osteoclast Biology

Dual effect of IL‐7/IL‐7R signalling on the osteoimmunological system: a potential therapeutic target for rheumatoid arthritis

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