IJUP08 - Universidade do Porto

Osteoclastic resorption of calcium phosphate based bone
substitutes: in vitro studies
C.A. Teixeira 1,2 , J. Costa-Rodrigues 1 , P.S. Gomes 1, Almeida Palmas, R. and M.H.
Fernandes 1
1 Laboratório de Farmacologia e Bicompatibilidade Celular, Faculty of Dental Medicine,
University of Porto, Portugal.
2 Faculty of Sciences, University of Porto, Portugal.
Bone is a dynamic tissue that undergoes constant remodelling, a process that requires a
perfect coordination between bone synthesis (mediated by osteoblasts) and bone resorption
(mediated by osteoclasts) [1]. Osteoclasts are specialized multinucleated cells derived from
the monocyte haematopoietic lineage. They adhere to bone matrix and promote bone
resorption through the secretion of acid and lytic enzymes. Deficiencies in osteoclast
number/function can lead to osteopetrosis, a disease characterized by bone deformities
caused by abnormal quantities of non-remodeled bone mass. On the other hand, increased
number and activity of osteoclasts may cause accelerated bone resorption, wich can lead to
osteoporosis (reviewed in [2]).
An essential property of bone substitutes is that they are integrated into the natural bone
remodelling process. Synthetic bone substitutes have numerous applications in medicine
and dental medicine. They promote bone repair and regeneration which makes them useful
tools in orthopedy, periodontal and maxillofacial surgery, and implantology. Calcium
phosphate based materials are the most commonly used, due to similarities with mineral
bone matrix.
Materials implanted in bone tissue must have adequate surface properties for normal cell
activity of bone remodelling. After implantation there is recruitment of osteoblastic
precursors to the material surface, followed by proliferation and differentiation, wich leads
to bone formation. This process is essential for osteointegration of the material. However,
the material should also allow a normal osteoclastic activity and must be resorbed by
cellular mechanisms. The balance between these two processes is essential for long term
survival of the implanted material [3].
In this work we will evaluate the proliferation and function of osteoclastic cells isolated
from human peripheral blood and cultivated in calcium phosphate based bone substitutes
with different surface characteristics. The characterization of osteoclast cultures in the
different conditions will be based on different parameters, namely: cell morphology and
adhesion, formation of multinucleated cells (osteoclastogenesis), formation of actin rings,
presence of vitronectin receptors (αVβ3 integrin), expression of specific osteoclastic
genes, tartrate resistant acid phosphatase activity, and formation of resorption lacunae.
References:
[1] Schilling A.F., Linhart W., Filke S., Gebauer M., Schinke T., Rueger J.M., Amling M. (2004)
Resorbability of bone substitute biomaterials by human osteoclasts. Biomaterials. 25 (18), 3963-
3972.
[2] Boyle W.J., Simonet W.S., Lacey D.L. (2003) Osteoclast differentiation and activation. Nature.
423 (6937), 337-342.
[3] Shen Z., Crotti T.N., McHugh K.P., Matsuzaki K., Gravallese E.M., Bierbaum B.E., Goldring S.R. (2006)
The role played by cell-substrate interactions in the pathogenesis of osteoclast-mediated peri-implant
osteolysis. Arthritis Res. Ther. 8 (3), R70.
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