Osteoporosis, a progressive bone disease characterized by decreased
bone mass and an increase in fractures, affects over 200 million people
worldwide. Most existing therapies such as bisphosphonate drugs reduce
the rate of bone loss, but they do not promote new bone growth.
Teriparatide (PTH) is the only agent currently approved for the
formation of new bone, but its use is limited to two years due to a
potential risk of osteosarcoma.
‘A new bone-forming growth factor, Osteolectin (Clec11a), might one day be a useful therapeutic option for osteoporosis and in regenerative medicine.’
A new bone-forming growth
factor, Osteolectin (Clec11a
), which reverses osteoporosis in mice and has implications for regenerative medicine has been discovered by a team of scientists at the Children's Medical Center Research
Institute at UT Southwestern (CRI).
Although Osteolectin is known to be made by certain bone marrow and
bone cells, CRI researchers are the first to show Osteolectin promotes
the formation of new bone from skeletal stem cells in the bone marrow.
The study, also found that deletion of Osteolectin in mice causes accelerated bone
loss during adulthood and symptoms of osteoporosis, such as reduced
bone strength and delayed fracture healing.
"These results demonstrate the important role Osteolectin plays in
new bone formation and maintaining adult bone mass. This study opens up
the possibility of using this growth factor to treat diseases like
osteoporosis," said Dr. Sean Morrison,
who led the team that made the discovery. Dr. Morrison, CRI Director,
holds the Mary McDermott Cook Chair in Pediatric Genetics at UT
Southwestern Medical Center, and the Kathryne and Gene Bishop
Distinguished Chair in Pediatric Research at Children's Research
Institute at UT Southwestern.
To determine whether treatment with Osteolectin could reverse bone
loss after the onset of osteoporosis, the CRI research team used mice
that had their ovaries removed to model the type of osteoporosis that
develops in postmenopausal women. Mice were given daily injections of
PTH or recombinant Osteolectin.
The study found that both recombinant
Osteolectin- and PTH-treated mice had significantly increased bone
volume compared to untreated mice. Both treatments effectively reversed
the bone loss that occurred after the removal of the ovaries.
"These early results are encouraging, suggesting Osteolectin might
one day be a useful therapeutic option for osteoporosis and in
regenerative medicine," said Dr. Morrison, also a Professor of
Pediatrics at UT Southwestern, a CPRIT Scholar in Cancer Research, and a
Howard Hughes Medical Institute Investigator.
Researchers in the Hamon Laboratory for Stem Cell and Cancer Biology,
of which Dr. Morrison is the principal investigator, plan to further
test Osteolectin's therapeutic potential and to identify the receptor
for Osteolectin, which is key to understanding the signaling mechanisms
the protein uses to promote osteogenesis.