Biomedical Engineering Reference
In-Depth Information
control osteoclastogenesis in a positive direction by increasing the expression
of RanK-L and decreasing the expression of OPG, or conversely, the
proportions can be reversed to decrease resorptive activity (Fig. 2.6c).
Once osteoclasts fully differentiate into mature cells, the bone-resorbing
activity and survival of these cells is regulated by RanK-L. The mature
osteoclast establishes a microenvironment between itself and the underlying
bone by peripherally attaching to the matrix using integrins.
75
This creates a
compartment between the ruffled basal border of the osteoclast and the bone
surface that is isolated from the general extracellular space.
76
an electrogenic
proton pump transports in h
+
ions to acidify the compartment which acts
to mobilize the mineralized component of bone. This exposes the organic
matrix which is subsequently degraded using proteases. The end result is
the removal of bone matrix and the development of characteristic Howship's
lacunae.
Osteoblast development follows a different course, beginning with
the local proliferation of Mscs residing in the bone marrow stroma and
periosteum (Fig. 2.5B). expression of the transcription factors runt-related
transcription factor-2 (Runx2), distal-less homeobox-5 (dlx5) and msh
homeobox homologue-2 (Msx2) are required to drive precursor cells toward
the osteoblast lineage and away from the adipocyte, myocyte and chondrocyte
lineages which are also derived by Mscs.
77-81
Once a precursor cell is
committed to the osteoblast lineage, the immature osteoblasts (also called
preosteoblasts) express type I collagen and bone sialoprotein (Bsp). Further
differentiation of the preosteoblast into a mature, bone-forming osteoblast
2.5
Lineage of osteoclasts and osteoblasts. (A) Osteoclasts are
derived from a hematopoeitic precursor in the bone marrow, spleen
or liver. Proliferation of mononuclear cells from the precursor
population requires M-CSF. The bloodborne preosteoclasts enter
the circulation and arrive at the site to be resorbed. They will fuse
together into a polykaryon only in the presence of M-CSF and
RANK-L. The immature osteoclast begins to express Trap, calcitonin
receptor (CTR), and the beta-3 (
b
3) integrin. RANK-L and a host of
transcription factors are required to push the cell into a mature
osteoclast phenotype, which maintains expression of many of the
same immature osteoclast markers. (B) Osteoblasts are derived from
a mesenchymal stem cell, which can also give rise to adipocytes,
myoblasts and chondrocytes. Proliferating precursors are pushed
toward the preosteoblast phenotype by the expression of Runx2,
Dlx5 and Msx2. The preosteoblast expresses collagen I (Col I) and
bone sialoprotein (BSP). Further, Runx2 expression, as well as osterix
and members of the Wnt signaling cascade (b-catenin, TCF/LEF1) are
required to achieve a mature, matrix-producing osteoblast phenotype
(Col I, osteocalcin (OC) and alkaline phosphatase expression).
Osteoblasts that become trapped in the matrix express E11, an early
osteocyte marker, and eventually express DMP-1, Mepe and SOST,
as the mature osteocyte phenotype is reached (reproduced with
permission of the Annual Reviews from Robling
et al
.
112
).
