ESPEYB16 5. Bone, Growth Plate and Mineral Metabolism Basic Science - Bone (3 abstracts)
5.18. Developmental origin, functional maintenance and genetic rescue of osteoclasts
Jacome-Galarza CE , Percin GI , Muller JT , Mass E , Lazarov T , Eitler J , Rauner M , Yadav VK , Crozet L , Bohm M , Loyher PL , Karsenty G , Waskow C & Geissmann F
Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA
Abstract: Nature. 2019 Apr;568(7753):541–545.
In brief: Murine knockout studies unravel the developmental origin of osteoclasts in embryonic, erythro-myeloid progenitors, acquiring exceptional longevity by constant fusion with monocytes and rejuvenation of cellular nucleii throughout postnatal life.
Comment: Osteoclast function is essential for bone metabolism. Malfunction of bone resorption, as seen in osteopetrosis, causes significant morbidity and often requires invasive treatments including bone marrow transplantation. Whilst monocytic differentiation of postnatal hematopoietic progenitors has been investigated in the last decades, the exact cellular origin of osteoclasts remains unclear (1).
Using multiple conditional murine knockout models, this study aimed to solve the decade-spanning quest for the true origin of osteoclasts. The authors identified a previously unknown embryonic origin of osteoclasts, undergoing continuous fusion with monocytes from peripheral blood. In these murine models, embryonic osteoclasts directly derived from erythro-myeloid progenitors (EMP) located in the bony anlagen. Furthermore, embryonic osteoclasts were essential for the optimal formation of long bones and membranous ossification, such as teeth eruption and skull growth.
The authors converted the findings of a novel mechanism of long-lived osteoclast with continuous acquisition of new nuclei into a new, cell-based therapeutic approach. They showed that transfusion of monocytic cells could rescue mice with an autosomal-recessive form of osteopetrosis. While textbook chapters on osteoclasts will have to be rewritten based on these novel findings, future studies are needed to prove the applicability of cell-based therapies in osteoclast-driven conditions, such as osteopetrosis.
Reference: 1. Xu, F. & Teitelbaum, S. L. Osteoclasts: New Insights. Bone Res. 1, 11–26 (2013).
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