Developmental origin, functional maintenance and genetic rescue of osteoclasts
Christian E. Jacome-Galarza,Gulce Itir Percin,James E. Muller,Elvira Mass,Elvira Mass,Tomi Lazarov,Jiri Eitler,Martina Rauner,Vijay K. Yadav,Lucile Crozet,Mathieu Bohm,Pierre-Louis Loyher,Gerard Karsenty,Claudia Waskow,Frederic Geissmann +14 more
TLDR
It is reported that osteoclasts that colonize fetal ossification centres originate from embryonic erythro-myeloid progenitors and are maintained after birth by fusion with circulating monocytes, and parabiosis or transfusion of monocytic cells results in long-term gene transfer in osteoclast in the absence of haematopoietic-stem-cell chimerism.Abstract:
Osteoclasts are multinucleated giant cells that resorb bone, ensuring development and continuous remodelling of the skeleton and the bone marrow haematopoietic niche. Defective osteoclast activity leads to osteopetrosis and bone marrow failure1–9, whereas excess activity can contribute to bone loss and osteoporosis10. Osteopetrosis can be partially treated by bone marrow transplantation in humans and mice11–18, consistent with a haematopoietic origin of osteoclasts13,16,19 and studies that suggest that they develop by fusion of monocytic precursors derived from haematopoietic stem cells in the presence of CSF1 and RANK ligand1,20. However, the developmental origin and lifespan of osteoclasts, and the mechanisms that ensure maintenance of osteoclast function throughout life in vivo remain largely unexplored. Here we report that osteoclasts that colonize fetal ossification centres originate from embryonic erythro-myeloid progenitors21,22. These erythro-myeloid progenitor-derived osteoclasts are required for normal bone development and tooth eruption. Yet, timely transfusion of haematopoietic-stem-cell-derived monocytic cells in newborn mice is sufficient to rescue bone development in early-onset autosomal recessive osteopetrosis. We also found that the postnatal maintenance of osteoclasts, bone mass and the bone marrow cavity involve iterative fusion of circulating blood monocytic cells with long-lived osteoclast syncytia. As a consequence, parabiosis or transfusion of monocytic cells results in long-term gene transfer in osteoclasts in the absence of haematopoietic-stem-cell chimerism, and can rescue an adult-onset osteopetrotic phenotype caused by cathepsin K deficiency23,24. In sum, our results identify the developmental origin of osteoclasts and a mechanism that controls their maintenance in bones after birth. These data suggest strategies to rescue osteoclast deficiency in osteopetrosis and to modulate osteoclast activity in vivo. Multinucleated osteoclasts required for normal bone development and tooth eruption in the mouse originate from embryonic erythro-myeloid progenitors and are maintained after birth by fusion with circulating monocytes.read more
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A lineage of myeloid cells independent of Myb and hematopoietic stem cells
Elisa Gomez Perdiguero,Christian Schulz,Laurent Chorro,Heather L. Szabo-Rogers,Nicolas Cagnard,Katrin Kierdorf,Marco Prinz,Bishan Wu,Jacobsen Sew.,Jeffrey W. Pollard,Jon Frampton,Karen J. Liu,Frederic Geissmann +12 more
TL;DR: Schulz et al. as discussed by the authors investigated whether adult macrophages all share a common developmental origin and found that a population of yolk-sac-derived, tissue-resident macophages was able to develop and persist in adult mice in the absence of hematopoietic stem cells.
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Materials design for bone-tissue engineering
TL;DR: In this paper, the authors provide an overview of materials-design considerations for bone-tissue-engineering applications in both disease modelling and treatment of injuries and disease in humans, and highlight scalable technologies that can fabricate natural and synthetic biomaterials (polymers, bioceramics, metals and composites) into forms suitable for bone tissue engineering applications in human therapies and disease models.
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Bone resorption restored in osteopetrotic mice by transplants of normal bone marrow and spleen cells : Osteopetrosis
TL;DR: This paper showed that mice with inherited osteopetrosis can recover bone and calcified cartilage by intravenous administration of cell suspensions prepared from spleen and bone marrow of normal littermates.
Journal ArticleDOI
Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption
Michelle M. McDonald,Michelle M. McDonald,Weng Hua Khoo,Weng Hua Khoo,Pei Ying Ng,Ya Xiao,Jad Zamerli,Peter Thatcher,Wunna Kyaw,Karrnan Pathmanandavel,Abigail K. Grootveld,Imogen Moran,Danyal Butt,Akira Nguyen,Alexander P. Corr,Alexander P. Corr,Sean C. Warren,Maté Biro,Natalie C. Butterfield,Siobhan E. Guilfoyle,Davide Komla-Ebri,Michael R.G. Dack,Hannah F. Dewhurst,John G. Logan,Yongxiao Li,Sindhu T. Mohanty,Sindhu T. Mohanty,Niall M. Byrne,Niall M. Byrne,Rachael L. Terry,Rachael L. Terry,Marija K. Simic,Marija K. Simic,Ryan C. Chai,Julian M.W. Quinn,Julian M.W. Quinn,Scott E. Youlten,Jessica A. Pettitt,David Abi-Hanna,David Abi-Hanna,Rohit Jain,Rohit Jain,Wolfgang Weninger,Wolfgang Weninger,Wolfgang Weninger,Mischa Lundberg,Mischa Lundberg,Shuting Sun,F H Ebetino,Paul Timpson,Woei Ming Lee,Paul A. Baldock,Paul A. Baldock,Michael J. Rogers,Michael J. Rogers,Robert Brink,Robert Brink,Graham R. Williams,J. H. Duncan Bassett,John P. Kemp,John P. Kemp,Nathan J. Pavlos,Peter I. Croucher,Peter I. Croucher,Tri Giang Phan,Tri Giang Phan +65 more
TL;DR: This article showed that osteomorphs are transcriptionally distinct from osteoclasts and macrophages and express a number of non-canonical osteoclast genes that are associated with structural and functional bone phenotypes when deleted in mice.
Journal ArticleDOI
Immune function and diversity of Osteoclasts in normal and pathological conditions
Maria-Bernadette Madel,Lidia Ibáñez,Abdelilah Wakkach,Teun J. de Vries,Anna Teti,Florence Apparailly,Claudine Blin-Wakkach +6 more
TL;DR: This review will address this novel vision of the OCL, not only as a phagocyte specialized in bone resorption, but also as innate immune cell participating in the control of immune responses.
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