Bone Cells

Osteoclasts
Osteoblasts
Osteocytes
Lining cells
Bone cell origins
Local regulators
Apoptosis

Introduction

There are two categories of bone cells. Osteoclasts are in the first category. They resorb (dissolve) the bone. The other category is the osteoblast family, which consists of osteoblasts that form bone, osteocytes that help maintain bone, and lining cells that cover the surface of the bone.


Osteoclasts


* . . . are large cells with many nuclei.
* . . . share lineage with blood cells (especially macrophages).
* Precursors circulate in the blood and bone marrow.
* Mature osteoclasts are formed from fusion of the precursors.
* This happens when RANK receptors on the osteoclast precursors are activated by the RANK-ligand which was secreted by osteoblasts.
* Osteoprotegerin (OPG) is a factor in the marrow which also binds RANK-ligand, so it can help to regulate the osteoclast activation.
* Osteoclasts resorb the bone. They form sealed compartments next to the bone surface and secrete acids and enzymes which degrade the bone. The edge next to the bone is called the ruffled border.
* After they finish resorbing bone, they undergo apoptosis (programmed cell death, sometimes called 'cell suicide'). This process is regulated by proteins from other cells.

Move your mouse over the photomicrograph below to see labels.
This picture is from the bones of a patient with very high
parathyroid hormone (PTH), so the osteoclasts are particularly easy to see.
PTH is further discussed in the hormone section.

photo courtesy of Russ Turner


Osteoblasts


*. . . are cuboidal and columnar in shape with a central nucleus found on the bone surface.
*Gap junctions with neighboring osteoblasts allow cells to communicate with each other.
*They come from bone marrow precursor cells. These precursors are capable of turning into either osteoblasts or fat cells, and various factors determine which kind of cells will be made. One of the factors is called Cbfa 1, which will cause the cell to differentiate into an osteoblast.
*The job of osteoblasts is to make the proteins that will form the organic matrix of bone and to control mineralization of the bone
*They have receptors for hormones such as vitamin D, estrogen, and parathyroid hormone.
*They secrete factors that activate osteoclasts (RANK-ligand) and other factors which communicate with other cells.
*They secrete PHEX, a protein that helps to regulate the amount of phosphate excreted by the kidney.
*When the team of osteoblasts has finished making new bone, some become surrounded with matrix and differentiate into osteocytes. Others will remain on the surface of the new bone and differentiate into lining cells. The rest undergo apoptosis (cell suicide) and disintegrate.

Move your mouse over the photomicrograph to see labels.


photo courtesy of Russ Turner


Osteocytes

* . . . live inside the bone and have long branches which allow them to contact each other as well as the lining cells on the bone surface.
* . . . are in a perfect position to sense any mechanical strain on the bone.
* . . . can secrete growth factors which activate the lining cells or stimulate the osteoblasts.
* Their exact role is still under investigation, but probably the osteocytes direct bone remodeling to accomodate mechanical strain and repair fatigue damage.

image from van der Plas and Nijweide, J Bone Mineral Res 1992, 7:389-96. Printed with permission from the ASBMR.

Lining cells

* . . . are former osteoblasts which have become flat and pancake-shaped.
* . . . line the entire surface of the bone.
* . . . are responsible for immediate release of calcium from the bone if the blood calcium is too low.
* . . . protect the bone from chemicals in the blood which dissolve crystals (such as pyrophosphate).
* . . . have receptors for hormones and factors that initiate bone remodeling.


Bone cell origins

This diagram summarizes the origins and fates of the bone cells. Mesenchymal refers to cells which were deep within the embryo during early development; some of them remain in the bone marrow but do not form blood cells. The hematopoietic cells form the liquid part of the bone marrow, and some of them circulate with the blood.


Local regulators

Bone cells produce molecules (usually proteins) that communicate with other cells. These molecules are called growth factors and cytokines. They act on nearby cells, and thus are considered local regulators. These factors control cell division (proliferation), differentiation, and survival.

Growth factors
Bone morphogenetic proteins (BMPs): BMPs are produced in the bone or bone marrow. They bind to BMP receptors that are on mesenchymal stem cells within the bone marrow. This causes the cells to produce Cbfa 1, which is a factor that activates the DNA so proteins can be made -- a process known as gene transcription. When Cbfa 1 activates the genes, the cells differentiate into mature osteoblasts. Without Cbfa 1, the cells would turn into fat cells instead!

Insulin-like growth factors (IGFs): These growth factors are produced by osteoblastic cells in response to several bone active hormones, such as parathyroid hormone and estrogens, or BMPs. IGFs accumulate in the bone matrix and are released during the process of bone remodeling by osteoclasts. IGFs stimulate osteoblastic cell replication -- in other words, they cause the osteoblasts to divide, forming new cells. They may also induce differentiation.

Cytokines
Interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF) family of cytokines: These factors are produced by osteoblastic cells in response to systemic hormones or other cytokines. IL-6 can cause:
* Bone marrow stem cells to differentiate into pre-osteoclasts
* Changes in proliferation and differentiation of osteoblasts
* Inhibition of apoptosis of osteoblasts

RANKL (RANK-ligand) is a cytokine that stays on the surface of osteoblast-related cells. The cells make RANKL in response to systemic hormones (such as 1,25dihydroxyvitamin D3) and cytokines (such as IL-6). Cell contact between RANKL-expressing osteoblastic cells and RANK-expressing osteoclast precursors induces osteoclast development, as shown in the animation in the osteoclast section.


Apoptosis

The mature bone is always remodeling: the old bone is resorbed and replaced with new bone. A team of osteoblasts and osteoclasts move along the bone, dissolving and rebuilding. What happens to the cells when they have finished rebuilding an area of bone? The osteoclasts and most of the osteoblasts undergo a process called apoptosis, or cell suicide. They are not killed. There is no lack of oxygen or nutrients. There are no toxic materials. Instead, there are genes in the cell which can be activated, causing the cell to disintegrate. These genes (of course) are carefully regulated within the cell. The factors that regulate apoptosis are currently under investigation. Some are related to estrogens, or to interleukins. Medications which could modify apoptosis have the potential for treating or preventing osteoporosis.


2003 by Merry Jo Oursler and Teresita Bellido
Updated 12/9/03

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