TY - JOUR
T1 - Osteoclast formation at the bone marrow/bone surface interface: Importance of structural elements, matrix, and intercellular communication
AU - Søe, Kent
AU - Delaissé, Jean-Marie
AU - Goldberg Borggaard, Xenia
PY - 2021/4
Y1 - 2021/4
N2 - Osteoclasts, the multinucleated cells responsible for bone resorption, have an enormous destructive power which demands to be kept under tight control. Accordingly, the identification of molecular signals directing osteo- clastogenesis and switching on their resorptive activity have received much attention. Mandatory factors were identified, but a very essential aspect of the control mechanism of osteoclastic resorption, i.e. its spatial control, remains poorly understood. Under physiological conditions, multinucleated osteoclasts are only detected on the bone surface, while their mono-nucleated precursors are only in the bone marrow. How are pre-osteoclasts targeted to the bone surface? How is their progressive differentiation coordinated with their approach to the bone surface sites to be resorbed, which is where they finally fuse? Here we review the information on the bone marrow distribution of differentiating pre-osteoclasts relative to the position of the mandatory factors for their differentiation as well as relative to physical entities that may affect their access to the remodelling sites. This info allows recognizing an “osteoclastogenesis route” through the bone marrow and leading to the coincident fusion/resorption site – but also points to what still remains to be clarified regarding this route and regarding the restriction of fusion at the resorption site. Finally, we discuss the mechanism responsible for the start of re- sorption and its spatial extension. This review underscores that fully understanding the control of bone re- sorption requires to consider it in both space and time - which demands taking into account the context of bone tissue.
AB - Osteoclasts, the multinucleated cells responsible for bone resorption, have an enormous destructive power which demands to be kept under tight control. Accordingly, the identification of molecular signals directing osteo- clastogenesis and switching on their resorptive activity have received much attention. Mandatory factors were identified, but a very essential aspect of the control mechanism of osteoclastic resorption, i.e. its spatial control, remains poorly understood. Under physiological conditions, multinucleated osteoclasts are only detected on the bone surface, while their mono-nucleated precursors are only in the bone marrow. How are pre-osteoclasts targeted to the bone surface? How is their progressive differentiation coordinated with their approach to the bone surface sites to be resorbed, which is where they finally fuse? Here we review the information on the bone marrow distribution of differentiating pre-osteoclasts relative to the position of the mandatory factors for their differentiation as well as relative to physical entities that may affect their access to the remodelling sites. This info allows recognizing an “osteoclastogenesis route” through the bone marrow and leading to the coincident fusion/resorption site – but also points to what still remains to be clarified regarding this route and regarding the restriction of fusion at the resorption site. Finally, we discuss the mechanism responsible for the start of re- sorption and its spatial extension. This review underscores that fully understanding the control of bone re- sorption requires to consider it in both space and time - which demands taking into account the context of bone tissue.
KW - Bone marrow
KW - Collagen network
KW - M-CSF
KW - Osteoclast
KW - Osteoclastogenesis
KW - RANKL
UR - https://publons.com/publon/33786463/
U2 - 10.1016/j.semcdb.2020.05.016
DO - 10.1016/j.semcdb.2020.05.016
M3 - Journal article
C2 - 32563679
SN - 1084-9521
VL - 112
SP - 8
EP - 15
JO - Seminars in Cell & Developmental Biology
JF - Seminars in Cell & Developmental Biology
ER -