Receptor activator of nuclear factor kappa B ligand antagonists inhibit tissue inflammation and bone loss in experimental periodontitis

Yukmijihwang-tang (YJ) has been used to treat diabetes mellitus, renal disorders, and cognitive impairment in traditional medicine. This study aimed to evaluate the anti-osteoporotic effect of YJ on ovariectomy (OVX)-induced bone loss in a rat and receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated osteoclast differentiation in bone marrow macrophages (BMMs). YJ reduced the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs) in an osteoclast/osteoblast co-culture system by regulating the ratio of RANKL/osteoprotegerin (OPG) by osteoblasts. Overall, YJ reduced TRAP-positive cell formation and TRAP activity and F-actin ring formation. Analysis of the underlying mechanisms indicated that YJ inhibited the activation of the nuclear factor of activated T cell cytoplasmic 1 (NFATc1) and c-Fos, resulting in the suppression of osteoclast differentiation-related genes such as TRAP, ATPase, H+ transporting, lysosomal 38 kDa, V0 subunit d2, osteoclast-associated receptor, osteoclast-stimulatory transmembrane protein, dendritic cell-specific transmembrane protein, matrix metalloproteinase-9, cathepsin K, and calcitonin receptor. YJ also inhibited the nuclear translocation of NFATc1. Additionally, YJ markedly inhibited RANKL-induced phosphorylation of signaling pathways activated in the early stages of osteoclast differentiation including the p38, JNK, ERK, and NF-κB. Consistent with these in vitro results, the YJ-administered group showed considerably attenuated bone loss in the OVX-mediated rat model. These results provide promising evidence for the potential novel therapeutic application of YJ for bone diseases such as osteoporosis.

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Receptor activator of nuclear factor-κB ligand and osteoprotegerin: maintaining the balance to prevent bone loss

Clinical Interventions in Aging ◽

10.2147/cia.s10153 ◽

2010 ◽

pp. 345 ◽

Cited By ~ 7

Author(s):

Vincent Goëb ◽

Trouvin Anne-Priscille

Keyword(s):

Bone Loss ◽

Nuclear Factor Kappa B ◽

Nuclear Factor ◽

Prevent Bone Loss ◽

Nuclear Factor Kappa ◽

Receptor Activator

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Artemisia annua extract prevents ovariectomy-induced bone loss by blocking receptor activator of nuclear factor kappa-B ligand-induced differentiation of osteoclasts

Scientific Reports ◽

10.1038/s41598-017-17427-6 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 9

Author(s):

Sun Kyoung Lee ◽

Hyungkeun Kim ◽

Junhee Park ◽

Hyun-Jeong Kim ◽

Ki Rim Kim ◽

...

Keyword(s):

Bone Loss ◽

Nuclear Factor Kappa B ◽

Artemisia Annua ◽

Nuclear Factor ◽

Induced Differentiation ◽

Nuclear Factor Kappa ◽

Receptor Activator

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Do anti-carbamylated protein antibodies in rheumatoid arthritis reflect local and systemic osteoporosis? A study of osteoprotegrin and receptor activator for nuclear factor kappa B ligand and radiological assessment

Egyptian Rheumatology and Rehabilitation ◽

10.1186/s43166-021-00067-0 ◽

2021 ◽

Vol 48 (1) ◽

Author(s):

Manal Shawky Hussein ◽

Rasha Ahmed Gaber ◽

Hala Mostafa Elsabagh ◽

Elsayed Mohamed Rageh

Keyword(s):

Rheumatoid Arthritis ◽

Bone Loss ◽

Disease Severity ◽

Nuclear Factor Kappa B ◽

Severe Disease ◽

Control Group ◽

Nuclear Factor ◽

Larsen Score ◽

Nuclear Factor Kappa ◽

Receptor Activator

Abstract Background One of the most important and dangerous complications of rheumatoid arthritis (RA) is bone loss, which manifested by erosions and juxta-articular or systemic bone loss. Anti-carbamylated protein (anti-CarP) antibodies which are also called anti-homocitrulline antibodies have recently been found in RA. Increase anti-CarP antibody titres may lead to severe disease and increase the progression of bone loss. Osteoprotegrin and receptor activator for nuclear factor kappa B and its ligand (RANKL) are the main players in the pathogenesis of osteoporosis. Thus, we aimed to investigate and detect the presence and prevalence of anti-CarP in rheumatoid arthritis and their association with disease severity and osteoporosis, as well as with OPG/RANKL in 80 Egyptian RA patients to highlight this relationship which could be useful in managing RA patients with osteoporosis. Results Serum anti-CarP levels were significantly increased in the RA group compared with the control group (P< 0.001). We found a negative association between anti-CarP and anti-CCP and disease activity (r=−0.878, −0.534, respectively, P<0.001). We also found a positive correlation between anti-CarP and the Larsen score, DEXA score, RF, HAQ, and RANKL (r=0.646, 0.287, 0.243, 0.892, 0.671, 0.869 [respectively], P<0.001) and there was negative correlation between anti-CarP and OPG (r=−0.553, P<0.001). Conclusion Anti-CarP antibodies are associated with disease severity and disability in RA patients. They could play an important and significant role in the pathogenesis of osteoporosis in these patients.

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