Implant surface properties
are a key factor in bone responses to
metallic bone implants. In view of the emerging evidence on the important
role of osteoclasts in bone regeneration, we here studied how surface
roughness affects osteoclastic differentiation and to what extent
these osteoclasts have stimulatory effects on osteogenic differentiation
of osteoprogenitor cells. For this, we induced osteoclasts derived
from RAW264.7 cell line and primary mouse macrophages on titanium
surfaces with different roughness (Ra 0.02–3.63
μm) and analyzed osteoclast behavior in terms of cell number,
morphology, differentiation, and further anabolic effect on osteoblastic
cells. Surfaces with different roughness induced the formation of
osteoclasts with distinct phenotypes, based on total osteoclast numbers,
morphology, size, cytoskeletal organization, nuclearity, and osteoclastic
features. Furthermore, these different osteoclast phenotypes displayed
differential anabolic effects toward the osteogenic differentiation
of osteoblastic cells, for which the clastokine CTHRC1 was identified
as a causative factor. Morphologically, osteoclast potency to stimulate
osteogenic differentiation of osteoblastic cells was found to logarithmically
correlate with the nuclei number per osteoclast. Our results demonstrate
the existence of a combinatorial effect of surface roughness, osteoclastogenesis,
and osteogenic differentiation. These insights open up a new dimension
for designing and producing metallic implants by considering the implant
roughness to locally regulate osseointegration through coupling osteoclastogenesis
with osteogenesis.