Cell Sub-Journal: Bone-promoting and bone-suppressing absorption Research has found new targets for anti-osteoporosis drugs!

In the course of life, the human body's bone tissue will be accompanied by bone formation mediated by osteoblasts and bone-breaking cell-mediated bone absorption and constantly updated, new bone formation at an early age is greater than absorption, adulthood tends to balance, in old age bone absorption is significantly greater than formation, osteoporosis is increasingly loose, especially in post-menopaomy women and elderly men.
most anti-osteoporosis drugs currently on the market can inhibit bone absorption, but few anabolic drugs promote bone formation, and most have side effects such as an increased risk of cardiovascular disease.
urgent need to gain insight into the mechanisms of bone development and regeneration to develop more effective and side-effect-free anti-osteoporosis drugs.
Recently, Professor Yue Rui of Tongji University in China published a new study in Cell Reports, they found a bone-forming inhibitor, known as fibroblast activated protein (Fap), inhibits its activity can promote bone production and inhibit bone absorption, is a new type of potential drug target for the treatment of osteoporosis.
is a new bone growth factor that reverses bone loss associated with osteoporosis.
to identify potential bone-forming regulators, the researchers used Osteolectin, an in-body expression mouse, to immune precipitation to identify their mutual protein: fibroblast-active protein (Fap).
further studies have found that Fap is a proline-specific serine protease, similar to Osteolectin's expression pattern, expressed highly in cartilage cells, bone marrow-to-bone cells (BMSC) and osteoblasts, among others, and that Osteolectin significantly inhibits The protease activity of Fap.
Osteolectin interacted with Fap to inhibit its protease activity To see if Fap played a role in bone development in young and aging mice, the researchers analyzed the bone espressopes of 8- and 10-month-old Fap mutant mice and found that Fap There was no effect on bone development in young mice, but The absence of Fap can significantly improve the volume reduction of the limb pine bone in the aging process in mice, so that the deposition rate and bone formation rate of squirrel bone minerals in mice increased significantly, bone-forming cells also showed an increasing trend, and bone-breaking cells decreased significantly.
Fap gene loss promoted bone formation in older mice, the researchers treated mice with the highly selective Fap inhibitor Ac-Gly-Boro-Pro (FAPi) to block the protease activity of their Fap, and found that The pharmacological inhibition of Fap also promoted bone formation and inhibited bone absorption in mice, increasing the number of bone cells and significantly reducing bone-breaking cells.
drug inhibition Of Fap can promote bone formation in young mice using transcriptional groups to promote bone formation and inhibit bone absorption after pharmacological inhibition of the molecular mechanism of in-depth study, found that FAPi treatment can promote the proliferation of BMSC in mice, The genes associated with the classical Wnt signaling path through which bone cell differentiation and bone formation are stimulated are significantly increased to promote bone formation, while the macrophages are inhibited from differentiating into bone-breaking cells, and the genes associated with the NF-B signaling path factor are significantly reduced to inhibit bone absorption.
Fap's pharmacological inhibition differences regulated by differentiation of osteoblasts and broken bone cells, the researchers constructed a model of osteoporosis induced by ovarian excision in mice, using FAPi treatment to test whether FAPi could be used to treat osteoporosis.
35 days of treatment, it was found that FAPi's inhibition of FAP reduced osteoporosis caused by ovarian excision.
compared with the control, the volume and connection density of the squirrel bone in the FAPi treated mice, as well as the mineral deposition rate and bone formation rate, increased significantly, and bone absorption was inhibited.
Fap inhibitors that reduce osteoporosis in ovarian mice also tested Osteolectin as an endogenetic inhibitor for Fap using the model animal zebrafish, and the results showed that Osteolectin could act as an endogenetic inhibitor for Fat to promote bone mineralization.
In short, the study identified for the first time a class of bone-forming inhibitors, fibroblast-activated proteins (Fap), whose protease activity is inhibited by the bone growth factor Osteolectin and can be used as a target for anti-osteoporosis drugs.
and the use of Fat inhibitors can promote bone production and inhibit bone absorption, promising to become a new class of anti-osteoporosis drugs! References: 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .