TY - JOUR
T1 - Nitrogen containing bisphosphonates impair the release of bone homeostasis mediators and matrix production by human primary pre-osteoblasts
AU - Giannasi, Chiara
AU - Niada, Stefania
AU - Farronato, Davide
AU - Lombardi, Giovanni
AU - Manfredi, Barbara
AU - Farronato, Giampietro
AU - Brini, Anna Teresa
PY - 2019/1/1
Y1 - 2019/1/1
N2 -
Bisphosphonates (BPs) represent the first-line treatment for a wide array of bone disorders. Despite their well-known action on osteoclasts, the effects they induce on osteoblasts are still unclear. In order to shed light on this aspect we evaluated the impact of two nitrogen containing bisphosphonates, Alendronate (ALN) and Zoledronate (ZOL), on human primary pre-osteoblasts. At first, we showed an inhibitory effect on cell viability and alkaline phosphatase activity starting from µM concentrations of both drugs. In addition, an inhibitory trend on mineralized nodules deposition was observed. Then low doses of both ALN and ZOL rapidly increased the release of the pro-inflammatory mediators TNFα and IL-1β, while increased DKK-1 and Sclerostin, both inhibitors of osteoblastogenesis. Finally, ALN and 10
-7
M ZOL decreased the expression of type I Collagen and Osteopontin, while both drugs slightly stimulated SPARC production. With these results, we would like to suggest a direct inhibitory action on bone-forming cells by nitrogen containing bisphosphonates.
AB -
Bisphosphonates (BPs) represent the first-line treatment for a wide array of bone disorders. Despite their well-known action on osteoclasts, the effects they induce on osteoblasts are still unclear. In order to shed light on this aspect we evaluated the impact of two nitrogen containing bisphosphonates, Alendronate (ALN) and Zoledronate (ZOL), on human primary pre-osteoblasts. At first, we showed an inhibitory effect on cell viability and alkaline phosphatase activity starting from µM concentrations of both drugs. In addition, an inhibitory trend on mineralized nodules deposition was observed. Then low doses of both ALN and ZOL rapidly increased the release of the pro-inflammatory mediators TNFα and IL-1β, while increased DKK-1 and Sclerostin, both inhibitors of osteoblastogenesis. Finally, ALN and 10
-7
M ZOL decreased the expression of type I Collagen and Osteopontin, while both drugs slightly stimulated SPARC production. With these results, we would like to suggest a direct inhibitory action on bone-forming cells by nitrogen containing bisphosphonates.
KW - Bisphosphonates
KW - Bone formation
KW - Human primary pre-osteoblasts
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UR - http://www.scopus.com/inward/citedby.url?scp=85060168284&partnerID=8YFLogxK
U2 - 10.7150/ijms.27470
DO - 10.7150/ijms.27470
M3 - Article
C2 - 30662325
AN - SCOPUS:85060168284
VL - 16
SP - 23
EP - 32
JO - International Journal of Medical Sciences
JF - International Journal of Medical Sciences
SN - 1449-1907
IS - 1
ER -