Osteoclasts

What are osteoclasts?

Osteoclasts are complex, multinucleated cells responsible for bone resorption, a process by which both the hard, mineral component of bone, as well as the flexible soft-tissue component of bone is broken down.

Bone as a tissue is continually renewing itself. This is necessary to allow it to adapt to the forces that act upon it and to allow it to repair cracks within it. In addition, our skeleton acts as a store for calcium, which is released from bone when blood calcium levels are too low.

For all three processes osteoclasts are required as they are the only cell type in our body that can dissolve the hard mineral of bone. Osteoclasts are one of three main cells types in bone.

The others are osteoblasts with as main function to build up bone and osteocytes with a key role as sensors for mechanical signals on the skeleton (Fig. 1).

Osteoclasts in boneFigure 1 - Osteoclasts in bone
A light microscopic image of bone cells in a young mammal.

1. Osteoclast, note how the cell is much larger than any of the other cells around. It has multiple nuclei and is formed through fusion of a number of osteoclast precursor cells. The cell is attached to a spicule of bone which is it degrading. This can be seen as the dark blue line, which is bone, is interrupted.

2. An osteoblast forming bone. The dark blue material is recently laid down bone and with time the cell may become embedded within it and become and osteocyte.

3. An osteocyte, almost completely surrounded by bone matrix, much of which it has produced itself when it was an active osteoblast.

4. The pink material is cartilage matrix. Long bones start life as cartilage and only over time become bone. The staining used here is Toluidine blue and this differentiates between cartilage (pink) and bone (blue).

5. Blue is bone matrix. Note another osteoblast on its way to becoming surrounded by bone.

6. Bone marrow cells.

Another important role for osteoclasts is during tooth eruption, allowing permanent teeth to erupt through the jaw bone and removing the roots of the baby teeth so they fall out (Fig. 2).

Osteoclasts and teethFigure 2 - Osteoclasts and teeth

These are images of a molar shedded from a young child. The roots of the tooth have been partly resorbed by osteoclasts and rather than wait for the whole process to complete, the child pulled out the tooth.

This allowed for examination of the resorption by microCT on the left, showing the drastic attack on the tooth roots. All this is achieved by osteoclasts alone.

On the right hand side a scanning electron micrograph shows the uneven surface of the tooth caused by osteoclasts removing bite-size bits of dentine.


Why study osteoclasts?

When osteoclasts work harder than they should bone loss will result. Examples of this are found in the diseases osteoporosis, cancer-induced bone disease, periodontitis, or rheumatoid arthritis.

There are also diseases in which osteoclasts do not work hard enough, such as in the condition osteopetrosis. In this inherited condition patients have a very dense, but also brittle, skeleton.


What are the questions Euroclast will address?

With the combined expertise of the research groups in Euroclast and their state-of-the-art facilities we can for the first time ask the following questions:

#1. Are all osteoclasts the same, or are there different populations of osteoclasts, for example in different types of bones, or in different types of disease?
Knowing this is important as it could influence how we understand and treat diseases caused by osteoclasts at different sites in our skeleton, or in different disease conditions.

#2. How exactly do osteoclasts work? What are the precise enzymes they use to break down the soft-tissue component of bone in different populations of osteoclasts?
There are already indications that osteoclasts in different bony sites preferentially use different enzymes. We need to more fully understand how osteoclasts work to be able to influence their activity in disease states.

#3. How do osteoclasts transport the enzymes and the acid they use to break down bone through the cell and out of the cell and how do they traffic the broken down bone through the cell to be secreted into the blood stream?
Basic knowledge in this area is important to more fully understand how osteoclasts are so uniquely able to resorb mineralised tissues.

#4. Do osteoclasts signal to osteoblasts to increase bone formation?
Understanding how osteoclasts influence osteoblasts to make more bone could lead to new ways to treat patients that suffer from low bone mass, such as in osteoporosis.