Molecular events caused by mechanical stress

in bone.
Nomura S
1
, Takano-Yamamoto T.
Author information
Abstract
The shape of bone changes as a result of bone remodeling corresponding to physical
circumstances such as mechanical stress. The tissue which receives the loaded mechanical stress
most efficiently is bone matrix. Recent studies revealed the function of osteocytes as
mechanosensors in the early stage of bone remodeling. Loaded mechanical stress is converted to
a series of biochemical reactions, and finally activates osteoclasts and osteoblasts to cause bone
resorption and formation. Biochemical and molecular biological studies have recently resulted in
the identification of the gene of which expression level is changed by mechanical stress. Nitric
oxide (NO) and cAMP is secreted in response to mechanical stress in the immediate early stage.
Genes encoding enzymes such as glutamate/aspartate transporter (GLAST), nitric oxide
synthetase (NOS) and prostaglandin G/H synthetase (PGHS-2) are identified as mechanical
stress-responsive. The expression level of IGF-I is enhanced under the control of PTH/PTHrP.
The expression of c-fos is increased by loading of mechanical stress. AP1, a heterodimer of c-
FOS/c-JUN, functions as a transcription factor of downstream gene(s). Elements including AP1
sites, cyclic AMP response elements (CRE) and shear stress response elements (SSRE) are found
in the promoter region of mechanical stress-response genes. The enhanced expression of
osteopontin (OPN) in the osteocytes of bone resorption sites was demonstrated by in situ
hybridization and immunohistochemistry and transdifferentiation of chondrocytes with the
abundant expression of BMP-2 and -4 in the process of distraction osteogenesis was observed.









[Recent progress in studies on osteocytes--
osteocytes and mechanical stress].
[Article in Japanese]
Hakeda Y
1
, Arakawa T, Ogasawara A, Kumegawa M.
Author information
Abstract
Although osteocytes are of the most abundant cells in bone, our knowledge about the role of
osteocytes in bone metabolism is still poor compared with that about osteoblasts and osteoclasts,
both being on the surface of bone. Osteocytes are terminally differentiated bone-forming cells.
During bone formation, some of the osteoblasts lining the surface of bone are incorporated into
the newly formed osteoid matrix and become osteocytes, while the other osteoblasts remain on
the surface as lining cells. During this transition from osteoblasts to osteocytes, the cells lose
numerous osteoblastic phenotypes and acquire osteocytic characteristics such as high expression
of osteocalcin and particularly their specific morphology. Osteocytes are connected with each
other in bone and with osteoblasts on the bone surface through canaliculi, forming cellular
networks; and gap-junctions present at the contact sites mediate their intercellular
communication. Several roles of osteocytes in bone have been proposed so far. Of them, based
on the morphological characteristics of osteocytes, sensation of mechanical stress loaded onto
bone is suspected to be one of their functions. One of the mechanical stresses on bone is fluid
shear stress. Between the osteocyte's plasma membrane and the bone matrix is the periosteocytic
space. This space exists both in the lacunae and in the canaliculi, and it is filled with extracellular
fluid (ECF). Application of mechanical stress to bone locally deforms the tissue. This periodical
deformation subsequently causes an increase in the flow of ECF in the periosteocytic space,
resulting in shear stress on the surface of the osteocytes. Experimental studies demonstrated that
bone cells were equivalently or more sensitive to the fluid shear stress than epithelial cells.
Osteocytic cells cultured enhanced expression of prostaglandin (PG) G/H synthase-2 (COX-2)
mRNA in response to shear stress. PGE2 is a potent regulator of proliferation and function of
osteoblasts and osteoclasts. Therefore, a metabolic response by osteoblasts and osteoclasts lining
the bone surface may be caused by PGE2 produced by osteocytes in response to shear stress
when the prostanoid reaches the surface through the canaliculi. In conclusion, osteocytes play an
important role in sensing extracellular mechanical stress, and the mechanical signals mediated by
osteocytes may regulate the overall metabolism of cells in bone tissue.