Psoralidin, a prenylated coumestan, as a novel anti-osteoporosis candidate to enhance bone formation of osteoblasts and decrease bone resorption of osteoclasts

Clearly osteoporosis is a major scourge of Western society but interest in the condition has risen exponentially in the last 10 years partly because of advances in our understanding of the disease process, the ability to predict its onset, to reverse the process of bone loss and to measure the consequences of treatment, but also in part due to increased public awareness. Further advances are likely, especially in our understanding of the genetic background of the disorder and our ability, not only to reduce bone resorption, but also to enhance bone formation. The challenge will be how to target our improved therapies at the expanding elderly population to reduce the impact and costs of fracture.

Download Full-text

Mushroom Extracts Decrease Bone Resorption and Improve Bone Formation

International Journal of Medicinal Mushrooms ◽

10.1615/intjmedmushrooms.v18.i7.10 ◽

2016 ◽

Vol 18 (7) ◽

pp. 559-569 ◽

Cited By ~ 2

Author(s):

Igor Erjavec ◽

Jelena Brkljacic ◽

Slobodan Vukicevic ◽

Boris Jakopovic ◽

Ivan Jakopovich

Keyword(s):

Bone Resorption ◽

Bone Formation ◽

Decrease Bone Resorption ◽

Mushroom Extracts

Download Full-text

Changes in bone metabolism associated with exposure to industrial vibration

Russian Journal of Occupational Health and Industrial Ecology ◽

10.31089/1026-9428-2019-59-9-766-767 ◽

2020 ◽

pp. 766-766

Author(s):

A. V. Sukhova ◽

E. N. Kryuchkova

Keyword(s):

Bone Mineral Density ◽

Alkaline Phosphatase ◽

Bone Resorption ◽

Bone Formation ◽

Bone Metabolism ◽

Biochemical Markers ◽

Mineral Density ◽

Local Vibration ◽

Markers Of Bone Formation

The influence of general and local vibration on bone remodeling processes is investigated. The interrelations between the long - term exposure of industrial vibration and indicators of bone mineral density (T-and Z-criteria), biochemical markers of bone formation (osteocalcin, alkaline phosphatase) and bone resorption (ionized calcium, calcium/creatinine) were established.

Download Full-text

Pharmacological inhibition of TAK1, with the selective inhibitor takinib, alleviates clinical manifestation of arthritis in CIA mice

Arthritis Research & Therapy ◽

10.1186/s13075-019-2073-x ◽

2019 ◽

Vol 21 (1) ◽

Cited By ~ 5

Author(s):

Scott A. Scarneo ◽

Liesl S. Eibschutz ◽

Phillip J. Bendele ◽

Kelly W. Yang ◽

Juliane Totzke ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Bone Resorption ◽

Bone Formation ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Inflammatory Diseases ◽

Cartilage Damage ◽

Cytokine Signaling ◽

Periosteal Bone Formation ◽

Bone Width

Abstract Objectives To examine the ability of takinib, a selective transforming growth factor beta-activated kinase 1 (TAK1) inhibitor, to reduce the severity of murine type II collagen-induced arthritis (CIA), and to affect function of synovial cells. Methods Following the induction of CIA, mice were treated daily with takinib (50 mg/kg) and clinical scores assessed. Thirty-six days post-CIA induction, histology was performed on various joints of treated and vehicle-treated animals. Inflammation, pannus, cartilage damage, bone resorption, and periosteal bone formation were quantified. Furthermore, pharmacokinetics of takinib were evaluated by LC-MS in various tissues. Rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) cells were cultured with 10 μM takinib and cytokine secretion analyzed by cytokine/chemokine proteome array. Cytotoxicity of takinib for RA-FLS was measured with 24 to 48 h cultures in the presence or absence of tumor necrosis factor (TNF). Results Here, we show takinib’s ability to reduce the clinical score in the CIA mouse model of rheumatoid arthritis (RA) (p < 0.001). TAK1 inhibition reduced inflammation (p < 0.01), cartilage damage (p < 0.01), pannus, bone resorption, and periosteal bone formation and periosteal bone width in all joints of treated mice compared to vehicle treated. Significant reduction of inflammation (p < 0.004) and cartilage damage (p < 0.004) were observed in the knees of diseased treated animals, with moderate reduction seen in the forepaws and hind paws. Furthermore, the pharmacokinetics of takinib show rapid plasma clearance (t½ = 21 min). In stimulated RA-FLS cells, takinib reduced GROα, G-CSF, and ICAM-1 pro-inflammatory cytokine signaling. Conclusion Our findings support the hypothesis that TAK1 targeted therapy represents a novel therapeutic axis to treat RA and other inflammatory diseases.

Download Full-text

The changes in bone turnover markers of female systemic lupus erythematousus patients without glucocorticoid

Lupus ◽

10.1177/09612033211000126 ◽

2021 ◽

Vol 30 (6) ◽

pp. 965-971

Author(s):

Wang Tianle ◽

Zhang Yingying ◽

Hong Baojian ◽

Gu Juanfang ◽

Wang Hongzhi ◽

...

Keyword(s):

Bone Resorption ◽

Bone Formation ◽

Bone Turnover ◽

Bone Metabolism ◽

Bone Turnover Markers ◽

Control Group ◽

Bone Resorption Marker ◽

Amino Terminal ◽

Normal People ◽

Turnover Markers

Objectives SLE is a chronic autoimmune disease, which can affect the level of bone metabolism and increase the risk of osteoporosis and fracture. The purpose of this research is to study the effect of SLE on bone turnover markers without the influence of glucocorticoids. Methods A total of 865 female subjects were recruited from Zhejiang Provincial People’s Hospital and the First Hospital of Jiaxing, including 391 SLE patients without the influence of glucocorticoids and 474 non-SLE people. We detected Bone turnover markers including amino-terminal propeptide of type 1 procollagen (P1NP), C-terminal turnover of β - I collagen (β-CTX), N-terminal midfragment of osteocalcin (NMID) and 25(OH)D, and analyzed the difference in Bone turnover markers between the SLE group and the control group, as well as the influence of age and season on bone metabolism in female SLE patients. Results In the SLE group, the average age was 43.93±13.95 years old. In the control group, the average age was 44.84±11.42 years old. There was no difference between the two groups (t = 1.03, P = 0.30). P1NP, NMID and 25(OH)D in the SLE group were significantly lower than those in the control group (Z = 8.44, p < 0.001; Z = 14.41, p < 0.001; Z = 2.19, p = 0.029), and β-CTX in the SLE group was significantly higher than that in the control group (Z = 2.61, p = 0.009). In addition, the levers of β-CTX, NMID, P1NP and 25(OH)D in older SLE female patients were statistically significantly higher than those in younger (ρ = 0.104, p = 0.041; ρ = 0.223, p < 0.001; ρ = 0.105, p = 0.038; ρ = 0.289, p < 0.001). Moreover, β-CTX reached a high value in summer and PINP reached a low value in winter. Conclusion The bone formation markers of female SLE patients without glucocorticoid were lower than those of normal people and the bone resorption marker was higher than that of normal people. The 25 (OH) D of female SLE patients without glucocorticoid was lower than that of normal people. The risk of osteoporosis and fracture may be higher in elderly women with SLE. The bone resorption level of female SLE patients is high in summer and the bone formation level is low in winter.

Download Full-text

The Development of Molecular Biology of Osteoporosis

International Journal of Molecular Sciences ◽

10.3390/ijms22158182 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8182

Author(s):

Yongguang Gao ◽

Suryaji Patil ◽

Jingxian Jia

Keyword(s):

Bone Resorption ◽

Molecular Biology ◽

Bone Formation ◽

Bone Mass ◽

Bone Remodeling ◽

Bone Cells ◽

Cell Activity ◽

Bone Cell ◽

Bone Disorders ◽

Molecular Aspects

Osteoporosis is one of the major bone disorders that affects both women and men, and causes bone deterioration and bone strength. Bone remodeling maintains bone mass and mineral homeostasis through the balanced action of osteoblasts and osteoclasts, which are responsible for bone formation and bone resorption, respectively. The imbalance in bone remodeling is known to be the main cause of osteoporosis. The imbalance can be the result of the action of various molecules produced by one bone cell that acts on other bone cells and influence cell activity. The understanding of the effect of these molecules on bone can help identify new targets and therapeutics to prevent and treat bone disorders. In this article, we have focused on molecules that are produced by osteoblasts, osteocytes, and osteoclasts and their mechanism of action on these cells. We have also summarized the different pharmacological osteoporosis treatments that target different molecular aspects of these bone cells to minimize osteoporosis.

Download Full-text

SLPI is a critical mediator that controls PTH-induced bone formation

Nature Communications ◽

10.1038/s41467-021-22402-x ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Akito Morimoto ◽

Junichi Kikuta ◽

Keizo Nishikawa ◽

Takao Sudo ◽

Maki Uenaka ◽

...

Keyword(s):

Parathyroid Hormone ◽

Bone Resorption ◽

Bone Formation ◽

Protease Inhibitor ◽

Bone Metabolism ◽

Serine Protease ◽

Serine Protease Inhibitor ◽

Secretory Leukocyte Protease Inhibitor ◽

Bone Imaging ◽

Genetic Ablation

AbstractOsteoclastic bone resorption and osteoblastic bone formation/replenishment are closely coupled in bone metabolism. Anabolic parathyroid hormone (PTH), which is commonly used for treating osteoporosis, shifts the balance from osteoclastic to osteoblastic, although it is unclear how these cells are coordinately regulated by PTH. Here, we identify a serine protease inhibitor, secretory leukocyte protease inhibitor (SLPI), as a critical mediator that is involved in the PTH-mediated shift to the osteoblastic phase. Slpi is highly upregulated in osteoblasts by PTH, while genetic ablation of Slpi severely impairs PTH-induced bone formation. Slpi induction in osteoblasts enhances its differentiation, and increases osteoblast–osteoclast contact, thereby suppressing osteoclastic function. Intravital bone imaging reveals that the PTH-mediated association between osteoblasts and osteoclasts is disrupted in the absence of SLPI. Collectively, these results demonstrate that SLPI regulates the communication between osteoblasts and osteoclasts to promote PTH-induced bone anabolism.

Download Full-text

Lumican Inhibits Osteoclastogenesis and Bone Resorption by Suppressing Akt Activity

International Journal of Molecular Sciences ◽

10.3390/ijms22094717 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4717

Author(s):

Jin-Young Lee ◽

Da-Ae Kim ◽

Eun-Young Kim ◽

Eun-Ju Chang ◽

So-Jeong Park ◽

...

Keyword(s):

Bone Resorption ◽

Bone Formation ◽

Map Kinases ◽

Osteoclast Differentiation ◽

Dependent Manner ◽

Dual Action ◽

Dose Dependent ◽

Resorptive Activity

Lumican, a ubiquitously expressed small leucine-rich proteoglycan, has been utilized in diverse biological functions. Recent experiments demonstrated that lumican stimulates preosteoblast viability and differentiation, leading to bone formation. To further understand the role of lumican in bone metabolism, we investigated its effects on osteoclast biology. Lumican inhibited both osteoclast differentiation and in vitro bone resorption in a dose-dependent manner. Consistent with this, lumican markedly decreased the expression of osteoclastogenesis markers. Moreover, the migration and fusion of preosteoclasts and the resorptive activity per osteoclast were significantly reduced in the presence of lumican, indicating that this protein affects most stages of osteoclastogenesis. Among RANKL-dependent pathways, lumican inhibited Akt but not MAP kinases such as JNK, p38, and ERK. Importantly, co-treatment with an Akt activator almost completely reversed the effect of lumican on osteoclast differentiation. Taken together, our findings revealed that lumican inhibits osteoclastogenesis by suppressing Akt activity. Thus, lumican plays an osteoprotective role by simultaneously increasing bone formation and decreasing bone resorption, suggesting that it represents a dual-action therapeutic target for osteoporosis.

Download Full-text