Report: Three easy steps to osteoporosis

[Guest guest]

ASCB 2002 - Day 4 - Wednesday 18 December 2002

Report:

Three easy steps to osteoporosis

Investigator: Bernard Halloran

18 December 2002

by Rabiya Tuma

Just three signaling factors regulate the complex

process that leads to osteoporosis, an expert from the University of

California in San Francisco reported today. But while others say the

work is significant, they remain skeptical of his simplistic hypothesis.

Bone maintenance is a balancing act between the

activity of osteoblasts, which form bone, and osteoclasts, which

reabsorb it. As animals age, the molecular signals exchanged between the

two cell types favor osteoclast activation, tipping the balance in favor

of bone loss, says Bernard Halloran.

The osteoclast-osteoblast system is controlled by

three signaling factors: RANK, a receptor that sits on the cell membrane

of osteoclasts; RANK ligand (RANKL), a membrane bound receptor protein

that sits on the membrane of osteoblasts, and OPG, a soluble protein

secreted by the osteoblasts.

When RANKL binds to RANK, the molecular connection

draws the two cells together and turns on the osteoclast, stimulating it

to chew away at the bone. On the other hand, if OPG binds to RANKL

first, then it blocks this cell-cell interaction and prevents osteoclast

activity, which allows the bones to continue to add material.

Halloran's new results suggest that since osteoblasts

manufacture both RANKL and OPG, they control the system. When he removed

osteoblasts and osteoclasts from young mice (6 weeks old), adult mice (6

months old), or old animals (24 months), and measured the amount of the

three proteins from each, the amount of RANKL increased with age, while

OPG decreased.

What's more, when Halloran cultured a mixture of old

osteoblasts with young osteoclasts, a large number of osteoclasts are

activated, he found. If he grows young osteoblasts with old osteoclasts,

fewer of the bone chewing cells activated.

Together, the expression pattern of the signaling

molecules and the cell culture data could explain why animals lose bone

mass with age, says Halloran. " The system is out of balance and can't

correct itself, " he told BioMedNet News.

However, not everyone who saw the data was compelled

by Halloran's hypothesis. Several researchers said the work is good as

far as it goes, but it is simplistic to think that just three signaling

factors could regulate a complex disease like osteoporosis, or a

biological system like bone maintenance.

" The work is definitely significant, " Branka Dabovic,

who studies cytokines and bone defects at New York University. " But

RANKL is not going to be the only factor controlling the balance; there

could be tens or hundreds of them. "

The real cause of bone loss will be understood,

Dabovic says, when we understand what induces the increase in RANKL

during the aging process.

Halloran agrees that the system portrayed by his

experiments seems rather simplistic, but says all of the factors that

are known to affect bone density, such as exercise, hormones, and diet,

seem to ultimately exert their influence through the RANKL signaling

pathway.

If someone could find a drug or therapy that can help

rebalance the OPG-RANKL system, he says, it could very likely help

prevent bone resorption.

Several companies are now developing and testing

synthetic forms of OPG to see if they can create a therapy for the

prevention or treatment of osteoporosis.