Complement and the recruitment of mononuclear osteoclasts.
OBJECTIVE
To investigate the hypothesis that complement mediates the recruitment of mononuclear osteoclast precursors to the exposed mineralised bone surface.


METHODS
Synthetic hydroxyapatite was incubated in vitro with fresh human serum, with and without complement activation inhibitors. Assays for complement components and the generation of the C3 breakdown product C3d were done. C3 deposition in human fetal tibia primary spongiosa was localised immunohistochemically and complement receptors CR1, CR2, CR3, and CR4 were localised cellularly. Immunohistochemical and enzyme histochemical characterisation of the mononuclear and multinuclear osteoclasts was made with emphasis on their association with complement C3 deposition.


RESULTS
Components of complement bind to synthetic hydroxyapatite crystals and, at lower concentrations, C3d was generated in the fluid phase. C3 was deposited in a focal and linear distribution on newly formed bone trabecular surfaces in the primary spongiosa. In a similar distribution CD61, CD68, and tartrate resistant acid phosphatase positive mononuclear osteoclasts were shown in close apposition to the bone trabecular surface. These mononuclear osteoclasts, unlike multinucleate osteoclasts, expressed the complement receptors CR3 and CR4. CR1 and CR2, however, could not be shown on either mononuclear or multinuclear osteoclasts.


CONCLUSIONS
It is suggested that C3 deposition on mineralised bone surfaces mediates the recruitment of mononuclear osteoclasts to this site. As the mononuclear osteoclasts fuse to form the multinucleate osteoclast, complement receptor expression is lost.
Mangham
D C
DC
Department of Pathology, Medical School, University of Birmingham, Edgbaston.
Scoones
D J
DJ
Drayson
M T
MT
D001846:Bone Development / Q000502:physiology*; D001842:Bone and Bones / Q000196:embryology; D003167:Complement Activation / Q000502:physiology; D003176:Complement C3 / Q000378:metabolism; D015933:Complement C3d / Q000096:biosynthesis; D003165:Complement System Proteins / Q000502:physiology*; D003460:Crystallization; D046508:Culture Techniques; D006801:Humans; D006882:Hydroxyapatites; D007150:Immunohistochemistry; D010010:Osteoclasts / Q000502:physiology*; D011951:Receptors, Complement / Q000032:analysis
D003176:Complement C3; D006882:Hydroxyapatites; D011951:Receptors, Complement; D015933:Complement C3d; D003165:Complement System Proteins