Abstract
(1) Background: In an adult skeleton, bone is constantly renewed in a cycle of bone resorption, followed by bone formation. This coupling process, called bone remodeling, adjusts the quality and quantity of bone to the local needs. It is generally accepted that osteoporosis develops when bone resorption surpasses bone formation. Osteoclasts and osteoblasts, bone resorbing and bone forming cells respectively, are the major target in osteoporosis treatment. Inside bone and forming a complex network, the third and most abundant cells, the osteocytes, have long remained a mystery. Osteocytes are responsible for mechano-sensation and -transduction. Increased expression of the osteocyte-derived bone inhibitor sclerostin has been linked to estrogen deficiency-induced osteoporosis and is therefore a promising target for osteoporosis management. (2) Methods: Recently we showed in vitro and in vivo that NMP (N-Methyl-2-pyrrolidone) is a bioactive drug enhancing the BMP-2 (Bone Morphogenetic Protein 2) induced effect on bone formation while blocking bone resorption. Here we tested the effect of NMP on the expression of osteocyte-derived sclerostin. (3) Results: We found that NMP significantly decreased sclerostin mRNA and protein levels. In an animal model of osteoporosis, NMP prevented the estrogen deficiency-induced increased expression of sclerostin. (4) Conclusions: These results support the potential of NMP as a novel therapeutic compound for osteoporosis management, since it preserves bone by a direct interference with osteoblasts and osteoclasts and an indirect one via a decrease in sclerostin expression by osteocytes.
Highlights
Osteoporosis is a common disease characterized by the deterioration of bone tissue and decreasing bone mass
(4) Conclusions: These results support the potential of N-methyl pyrrolidone (NMP) as a novel therapeutic compound for osteoporosis management, since it preserves bone by a direct interference with osteoblasts and osteoclasts and an indirect one via a decrease in sclerostin expression by osteocytes
While there is a diverse armamentarium to serve as inhibitors of the osteoclastic activity, parathyroid hormone (PTH) was the first anabolic agent approved by the FDA (Food and Drug Administration (USA)) [5] for the treatment of osteoporosis in 2002
Summary
Osteoporosis is a common disease characterized by the deterioration of bone tissue and decreasing bone mass This results in increased bone fragility and higher fracture risk, at the hip, spine and wrist [1]. Even though osteoporosis causes an increased osteoclastic bone resorption activity surpassing the rate of osteoblastic bone formation, most of the above-mentioned treatments are targeting only one of the involved cell type. Sclerostin—mainly produced by osteocytes—is encoded by the SOST (Sclerosteosis) gene on chromosome 17 in humans [30], is a negative regulator of bone formation and an important regulator of bone mass [31] It binds to the LRP5/6 receptor and Frizzled co-receptor on the osteoblast cell surface, thereby interfering with Wnt ligand binding and blocking osteoblast differentiation and activity [32]. FFoolllloowwiinngg uuppononouor ufirndfiinngdsinsghsowshinogwtihnagt NthMaPt iNnhMibPitsinohstibeoitcslaoststdeioffcelraesnt tidaitfifoenre[n9]t,iaimtiopnrov[9e]s, iomstpeorobvlaesst odsitfefeorbelnatsitatdioifnfearnendtiinatciroenasaensdboinncerereagseens ebroantieonre[g1e0n],etrhaetiponre[s1e0n]t, stthuedpyraeismenetdsttoudevyaaluimateedthtoe eevffaelcutaotfeNthMe PefofenctoostfeNocMytPeso.n osteocytes
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