Identification of important interactions between subchondral bone ...

CHAPTER 2: Introduction
Bone is a specialized tissue, which together with cartilage make up the human skeleton. The
bones have three main functions; 1) providing mechanical support for the whole body and acting
as muscle attachment for locomotion, 2) providing protective shields for the vital organs and the
bone marrow, and 3) providing a reserve for ions, mainly calcium and phosphate, and for growth
factors and cytokines 15,16 .
There are several subtypes of bones; long bone, flat bones, short bones and
irregular bones 17 , of which only long bones - e.g. femur and tibia, which constitute the knee - will
be discussed further in this thesis. Long bones are developed by endochondral ossification as
shown in fig. 2A 18 . This whole process starts with a condensation of mesenchymal cells to form
the cartilage anlage of the future bone. The mesenchymal cells further proliferate and
differentiate into chondroblasts. The chondroblasts produce a cartilaginous matrix, where the
predominant collagen is collagen type II. The chondroblasts become progressively embedded
within their own matrix, where they lie within lacunae, and they are then called chondrocytes (the
only cell type in articular cartilage). Eventually, the chondrocytes may further differentiate into
hypertrophic chondrocytes whereby the cartilage becomes calcified before the hypertrophic
chondrocytes undergo apoptosis and then disappear from the lacunae. This generates the primary
ossification-centre, which splits into two opposite growth plates that moves from the centre of
the long bone, towards the ends. At this stage of bone development, the blood vessels penetrate
the calcified matrix supplying osteoclast precursors. Differentiated osteoclasts (bone resorbing
cells) use the lacunas in the calcified cartilage matrix as templates to initiate resorption.
Fig. 2. Development of long bone by endochondral ossification. Schematic diagram showing the initial
stages of endochondral ossification. A) Endochondral ossification is initiated from accumulated mesenchymal
cells, which continue to differentiate and starts forming the primary, and then later the two secondary
ossification centres. Trabecular bone is present after several cycles of remodelling 16 . B) The growth plate
between the epiphysis and diaphysis is enlarged and divided in the different zones. The growth plate
demonstrates the different stages of chondrocyte differentiation involved in endochondral bone formation.
The figure was produced by Madsen, S.H.
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