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Deletion of the membrane complement inhibitor CD59a drives age and gender-dependent alterations to bone phenotype in mice.

Bloom AC, Collins FL, Van't Hof RJ, Ryan ES, Jones E, Hughes TR, Morgan BP, Erlandsson M, Bokarewa M, Aeschlimann D, Evans BA, Williams AS - Bone (2015)

Bottom Line: A recent study suggested a role for the complement membrane attack complex in experimental models of osteoarthritis.Our data reveal, for the first time, that CD59a is a regulator of bone growth and homeostasis.CD59a ablation in male mice results in longer and wider bones, but with less density, which is likely a major contributing factor for their susceptibility to osteoarthritis.

View Article: PubMed Central - PubMed

Affiliation: Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK.

No MeSH data available.


Related in: MedlinePlus

Reduced osteoid and increased bone formation in male CD59a-deficient mice at 8 weeks of age. Femurs were stained with von Kossa/van Gieson to reveal osteoids. (A) Histomorphometric investigation of femoral osteoid surface over total bone surface (OS/BS) of WT (black bars) and CD59a−/− (white bars) male mice at 8 and 20 weeks. All values are mean ± SEM from a minimum of six mice per group at 8 and 20 weeks of age. ⁎⁎⁎P < 0.001 versus WT. (B) Representative images of osteoid staining with van Gieson (pink appearance and highlighted by arrows) at 8 weeks. M, marrow; Tb, trabecular bone. Scale bar (black), 100 μm. (C) Mineral apposition rate (MAR) and (D) bone formation rate (BFR/BS) calculated from calcein double labelling are shown in WT (black bars) and CD59a−/− (white bars) mice. Bone formation rate is the amount of mineralised bone formed per unit of time per unit of bone surface. All values are mean ± SEM from four mice per group at 8 weeks of age. ⁎P < 0.05 versus WT. (E) Representative images of calcein double labelling in WT and CD59a−/− mice. Scale bar (white), 100 μm.
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f0025: Reduced osteoid and increased bone formation in male CD59a-deficient mice at 8 weeks of age. Femurs were stained with von Kossa/van Gieson to reveal osteoids. (A) Histomorphometric investigation of femoral osteoid surface over total bone surface (OS/BS) of WT (black bars) and CD59a−/− (white bars) male mice at 8 and 20 weeks. All values are mean ± SEM from a minimum of six mice per group at 8 and 20 weeks of age. ⁎⁎⁎P < 0.001 versus WT. (B) Representative images of osteoid staining with van Gieson (pink appearance and highlighted by arrows) at 8 weeks. M, marrow; Tb, trabecular bone. Scale bar (black), 100 μm. (C) Mineral apposition rate (MAR) and (D) bone formation rate (BFR/BS) calculated from calcein double labelling are shown in WT (black bars) and CD59a−/− (white bars) mice. Bone formation rate is the amount of mineralised bone formed per unit of time per unit of bone surface. All values are mean ± SEM from four mice per group at 8 weeks of age. ⁎P < 0.05 versus WT. (E) Representative images of calcein double labelling in WT and CD59a−/− mice. Scale bar (white), 100 μm.

Mentions: Osteoclasts and osteoblasts act in a dynamic equilibrium as part of the bone remodelling unit in which osteoblasts secrete bone matrix [25]. When osteoblast activity was analysed by measuring osteoid surface/bone surface (OS/BS), in male CD59a−/− mice at 8 weeks of age, OS/BS ratio was two-fold lower than in WT secondary spongiosa (Figure 5A and B). By 20 weeks, the OS/BS in WT mice was significantly reduced compared to 8 weeks and was not significantly different from the OS/BS in CD59a−/− mice, the latter stayed unchanged between the time points (Figure 5A). MAR and BFR/BS were determined in vivo from double labelling with calcein (Figure 5C–E); both were significantly increased (MAR: 30%; BFR/BS: 60%) in the secondary spongiosa of CD59a−/− compared to WT mice at 8 weeks of age. The increased calcein double label width of CD59a−/− mice is clearly visible in Figure 5E. No adverse effects were observed.


Deletion of the membrane complement inhibitor CD59a drives age and gender-dependent alterations to bone phenotype in mice.

Bloom AC, Collins FL, Van't Hof RJ, Ryan ES, Jones E, Hughes TR, Morgan BP, Erlandsson M, Bokarewa M, Aeschlimann D, Evans BA, Williams AS - Bone (2015)

Reduced osteoid and increased bone formation in male CD59a-deficient mice at 8 weeks of age. Femurs were stained with von Kossa/van Gieson to reveal osteoids. (A) Histomorphometric investigation of femoral osteoid surface over total bone surface (OS/BS) of WT (black bars) and CD59a−/− (white bars) male mice at 8 and 20 weeks. All values are mean ± SEM from a minimum of six mice per group at 8 and 20 weeks of age. ⁎⁎⁎P < 0.001 versus WT. (B) Representative images of osteoid staining with van Gieson (pink appearance and highlighted by arrows) at 8 weeks. M, marrow; Tb, trabecular bone. Scale bar (black), 100 μm. (C) Mineral apposition rate (MAR) and (D) bone formation rate (BFR/BS) calculated from calcein double labelling are shown in WT (black bars) and CD59a−/− (white bars) mice. Bone formation rate is the amount of mineralised bone formed per unit of time per unit of bone surface. All values are mean ± SEM from four mice per group at 8 weeks of age. ⁎P < 0.05 versus WT. (E) Representative images of calcein double labelling in WT and CD59a−/− mice. Scale bar (white), 100 μm.
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f0025: Reduced osteoid and increased bone formation in male CD59a-deficient mice at 8 weeks of age. Femurs were stained with von Kossa/van Gieson to reveal osteoids. (A) Histomorphometric investigation of femoral osteoid surface over total bone surface (OS/BS) of WT (black bars) and CD59a−/− (white bars) male mice at 8 and 20 weeks. All values are mean ± SEM from a minimum of six mice per group at 8 and 20 weeks of age. ⁎⁎⁎P < 0.001 versus WT. (B) Representative images of osteoid staining with van Gieson (pink appearance and highlighted by arrows) at 8 weeks. M, marrow; Tb, trabecular bone. Scale bar (black), 100 μm. (C) Mineral apposition rate (MAR) and (D) bone formation rate (BFR/BS) calculated from calcein double labelling are shown in WT (black bars) and CD59a−/− (white bars) mice. Bone formation rate is the amount of mineralised bone formed per unit of time per unit of bone surface. All values are mean ± SEM from four mice per group at 8 weeks of age. ⁎P < 0.05 versus WT. (E) Representative images of calcein double labelling in WT and CD59a−/− mice. Scale bar (white), 100 μm.
Mentions: Osteoclasts and osteoblasts act in a dynamic equilibrium as part of the bone remodelling unit in which osteoblasts secrete bone matrix [25]. When osteoblast activity was analysed by measuring osteoid surface/bone surface (OS/BS), in male CD59a−/− mice at 8 weeks of age, OS/BS ratio was two-fold lower than in WT secondary spongiosa (Figure 5A and B). By 20 weeks, the OS/BS in WT mice was significantly reduced compared to 8 weeks and was not significantly different from the OS/BS in CD59a−/− mice, the latter stayed unchanged between the time points (Figure 5A). MAR and BFR/BS were determined in vivo from double labelling with calcein (Figure 5C–E); both were significantly increased (MAR: 30%; BFR/BS: 60%) in the secondary spongiosa of CD59a−/− compared to WT mice at 8 weeks of age. The increased calcein double label width of CD59a−/− mice is clearly visible in Figure 5E. No adverse effects were observed.

Bottom Line: A recent study suggested a role for the complement membrane attack complex in experimental models of osteoarthritis.Our data reveal, for the first time, that CD59a is a regulator of bone growth and homeostasis.CD59a ablation in male mice results in longer and wider bones, but with less density, which is likely a major contributing factor for their susceptibility to osteoarthritis.

View Article: PubMed Central - PubMed

Affiliation: Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK.

No MeSH data available.


Related in: MedlinePlus