Recent discovery show
The osteocytes are
metabolically active and multifunctional, response to mechanical forces apply
to the bone
It also respond to reduced
mechanical stress like immobilization , muscles weakness
Weightlessness in space
Clinical anatomy
: Osteocyte cell death can occur in association with pathologic conditions such
as osteoporosis and osteoarthritis, which leads to increased skeletal
fragility, linked to the loss of ability to sense microdamage and/or signal
repair. Oxygen deprivation that occurs as the result of immobilization (bed
rest), glucocorticoid treatment, and withdrawal of oxygen have all been shown
to promote osteocyte apoptosis
Role of osteocytes in multiple myeloma bone disease:
Multiple myeloma bone disease is characterized by exacerbated
bone resorption and the presence of osteolytic lesions that do not heal because
of a concomitant reduction in bone formation. Osteocytes produce molecules that
regulate both bone formation and resorption. Recent findings suggest that the
life span of osteocytes is compromised in multiple myeloma patients with bone
lesions. In addition, multiple myeloma cells affect the transcriptional profile
of osteocytes by upregulating the production of pro-osteoclastogenic cytokines,
stimulating osteoclast formation and activity. Further, patients with active
multiple myeloma have elevated circulating levels of sclerostin, a potent
inhibitor of bone formation which is specifically expressed by osteocytes in
bone.
How osteocytes respond to mechanical stimuli
Mechanical force of bone (
during walking ) cause flow of interstitial fluid out of the canaliculi and
lacunae on the compressed side of the bone .
Movement of interstitial
fluid generates a transient electrical potential . this transient electrical
potential opens voltage gated calcium channels in the membrane of osteocytes
over which tissue fluid flow
Resulting increase in
intracellular calcium , ATP , nitric oxide concentration and prostaglandin E 2 synthesis alter
expression of genes responsible for bone formation.
the stess
region of bone will have the largest deposition of new bone
When mechanical
stresses are reduce, osteocytes secrete matrix metalloproteinases (MMPs) which
degrade bone matrix
Only recently was the complexity of the osteocyte network
even described. These cells grow out in the bone space, interacting with ion
signals through long dendritic processes, creating a fascinating system of
intercellular connections. These cells interact not only with each other but
also with vasculature, osteoblasts, osteoclasts, and marrow cells. It has long
been argued such a network simply must have a function, and while this is now
almost undeniably true the full extent of its purpose remains an area of much
investigation
Dr Bonewald’s 2011 review in the
Journal of Bone and Mineral Research, “The Amazing Osteocyte”, describes just a
handful of the proven roles osteocytes play not just in bone health and
homeostasis, but also their role in a much broader signaling network.
- Osteocytes not only possess potential to activate
osteoblasts, but also osteoclasts, essentially regulating both sides of
the bone anabolism/catabolism balance.\
- Osteocyte death leads to inflammation and bone
fragility.
- Wnt/b-catenin regulate osteocyte function (whereas
previously osteocytes hadn’t been considered important in bone
regulation).
- Osteocytes are a source of minerals and factors, like
Calcium, FGF-23, and Dmp1, which signal not just to other bone cells but
in an endocrine fashion to many other organs.
Osteocytes play a mechanosensory role. The
dendritic network of osteocytes allows communication across large areas of
bone, and these cells are subject to all the stress and
