D-chiro-inositol Negatively Regulates the Formation of Multinucleated Osteoclasts by Down-Regulating NFATc1

Abstract

We have shown that D-chiro-inositol is negatively involved in osteoclastogenesis through the inhibition of multinucleated OC formation by cell-cell fusion. The expression of NFATc1 was significantly down-regulated by D-chiro-inositol in OCs and consequently, the expression of OC marker genes was significantly reduced. Hence, these results show that D-chiro-inositol might be a good candidate to treat inflammatory bone-related diseases or secondary osteoporosis in diabetes mellitus.

Secretion of a Truncated Osteopetrosis-associated Transmembrane Protein 1 (OSTM1) Mutant Inhibits Osteoclastogenesis through Down-regulation of the B Lymphocyte-induced Maturation Protein 1 (BLIMP1)-Nuclear Factor of Activated T Cells c1 (NFATc1) Axis

“…General chemicals were purchased from Sigma-Aldrich. The Raw264.7 (murine monocytic cell line), NIH3T3 (murine fibroblastic cell line), 293T (human kidney cell line), KMls-8.3.5.1 (murine T-cell hybridoma), S2 (Drosophila cells), MC3T3-E1 (murine osteoblastic cell line), and UAMS32 (murine osteoblastic cell line) cell lines and primary OBs (pOBs) were prepared and maintained as described previously (12)(13)(14). The mice were purchased from Daehan Biolink Co. (Umsung, Korea), and the animal study was approved (approval no.…”

“…CNU-00114) through the Animal Experiment Ethics Committee of Chungnam National University. For the retroviral expression plasmids, the full-length ORF (aa 1-338, pMX-puro-OSTM1) and truncated form (aa 1-268, pMX-puro-OSTM1⌬TM) of the murine Ostm1 gene were amplified through RT-PCR and subcloned into retroviral vector pMX-puro-FLAG (13). Retroviral plasmids expressing the constitutively active form of NFATc1 (caNFATc1), c-Fos, and BLIMP1 were prepared as described previously (12,15,16).…”

“…Osteoclastogenesis-Bone marrow (BM)-derived macrophages (BMMs) and BM-derived OCs (BMOCs) were prepared as described previously (13). Briefly, BM cells were collected from the tibia and femur of 6 -8-week-old C57BL/6 male mice and cultured in ␣-minimal essential medium containing 10% FBS and 5 ng/ml of M-CSF overnight.…”

“…Analysis of OCs-OCs were analyzed as described previously (13). Briefly, OCs were fixed with 10% formalin for 10 min and permeabilized in an ethanol/acetone (1:1) mixture for 1 min.…”

The “Other” Inositols and Their Phosphates: Synthesis, Biology, and Medicine (with Recent Advances inmyo‐Inositol Chemistry)

“…D-chiro-Inositol has been shown to inhibit cell-cell fusion and the expression of several osteoclastogenic genes by downregulating nuclear factor of activated T cells c1. [96] The insecticide DDT, when fed to rats, causes increases in liver weight and hepatic lipids. The co-administration with DDT of 1L-chiro-or 1D-chiro-inositol promotes this effect.…”