Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

FIBROBLASTS AND THEIR TRANSFORmationS: THE CONNECTIVE-TISSUE CELL FAMILY
1229
stiff
extracellular
matrix
YAP on TAZ on
bone cell
soft extracellular
matrix
YAP off TAZ off
fat cell
A class of connective-tissue cells in the bone marrow, called bone marrow stromal
cells, provides an example of radical connective-tissue versatility. These cells,
which can be regarded as a kind of fibroblast, can be isolated from the bone marrow
and propagated in culture. MBoC6 Large n22.107/22.12
clones of progeny can be generated in this
way from single ancestral stromal cells. Depending on the culture conditions, the
members of such a clone either can continue proliferating to produce more cells
of the same type, or can differentiate as fat cells, cartilage cells, or bone cells. The
fate of the cells depends on physical as well as chemical signals: embedded in a
stiff, unyielding matrix, they tend to turn into bone cells, whereas in a softer, more
elastic matrix, they tend to turn into fat cells. This effect is mediated by an intracellular
pathway that responds to tension in actin–myosin bundles and relays a
signal to specific transcription regulators in the nucleus (Figure 22–12). Because
of their self-renewing, multipotent character, the bone marrow stromal cells, and
other cells with similar properties, are referred to as mesenchymal stem cells.
Figure 22–12 Control of fibroblast
differentiation by the physical properties
of the extracellular matrix. On a stiff
matrix, the cells form strong adhesions,
spread out, and tend to turn into bone
cells. On a soft matrix, where the cells are
unable to form strong anchorages, they fail
to spread and tend to differentiate as fat
cells. These effects depend on transcription
regulators (yap and taZ proteins) that
move into the cell nucleus in response to
tension developed in actin–myosin bundles
in the cytoplasm. (Based on S. Dupont et
al., Nature 474:179–183, 2011.)
Osteoblasts Make Bone Matrix
Cartilage and bone are tissues of very different character; but they are closely
related in origin, and the formation of the skeleton depends on an intimate partnership
between them.
Cartilage tissue is structurally simple, consisting of cells of a single type—
chondrocytes—embedded in a more or less uniform, highly hydrated matrix consisting
of proteoglycans and type II collagen (discussed in Chapter 19). The cartilage
matrix is deformable, and the tissue grows by expanding as the chondrocytes
divide and secrete more matrix (Figure 22–13). Bone, by contrast, is dense and
rigid; it grows by apposition—that is, by deposition of additional matrix on free
surfaces. Like reinforced concrete, the bone matrix is predominantly a mixture of
tough fibers (type I collagen fibrils), which resist pulling forces, and solid particles
(calcium phosphate as hydroxylapatite crystals), which resist compression. The
bone matrix is secreted by osteoblasts that lie at the surface of the existing matrix
and deposit fresh layers of bone onto it. Some of the osteoblasts remain free at the
surface, while others gradually become embedded in their own secretion. This
freshly formed material (consisting chiefly of type I collagen) is rapidly converted
into hard bone matrix by the deposition of calcium phosphate crystals in it.
Once imprisoned in hard matrix, the original bone-forming cell, now called
an osteocyte, has no opportunity to divide, although it continues to secrete additional
matrix in small quantities around itself. The osteocyte, like the chondrocyte,
occupies a small cavity, or lacuna, in the matrix, but unlike the chondrocyte
dividing
chondrocyte
freshly secreted
matrix
CARTILAGE EXPANDS
matrix
Figure 22–13 The growth of cartilage.
The tissue expands as the chondrocytes
divide and make more matrix. The freshly
synthesized matrix with which each cell
surrounds itself is shaded dark green.
Cartilage may also grow by recruiting
fibroblasts from the surrounding tissue and
converting them into chondrocytes.