EFFECTIVENESS OF KATUK LEAVES ETHANOL EXTRACT AMOUNT OF OSTEOBLAST AND OSTEOCLAST ON ALVEOLAR BONE IN ORTHODONTIC TREATMENT Research On Alveolar Bone Of Guinea Pigs

The optimal achievement of orthodontic treatment is determined by a bone remodelling process involving osteoblast, osteoclasts, and the estrogen hormone. Estrogen deficiency can increase osteoclast age and decrease osteoblast, resulting in an imbalance between osteoclasts and osteoblasts. One natural alternative that can replace the role of the hormone estrogen is phytoestrogens. Sauropus androgynus (L.) Merr (katuk) is a phytoestrogen that contains isoflavones with many similarities with estrogens. This research aims to determine the effectiveness of the various doses of ethanol extract of katuk leaves orally on the number of osteoblasts and osteoclasts. This research was conducted using experimental laboratory methods using 24 female Guinea pigs divided into a control group and three groups with various doses of 39.15 mg/BW, 78.3 mg/BW, and 156.5 mg/BW. The observations made in this test were the number of osteoblasts and osteoclasts on the alveolar guinea pig on day 14 and analysed using the one way ANOVA test (p <0.05). All guinea pigs have applied a rubber separator to the left incisor and given a dose according to the group, and after 14th days, histological preparations were made. The results showed that the highest number of osteoblasts was at a dose of 78.3 mg/BW, and the lowest number of osteoclasts was at a dose of 39.15 mg/BW with values of 15.03 ± 2.27 and 1.73 ± 0.56, respectively. Statistically, the number of osteoblasts between the treatment and control groups significantly differed (p = 0.04), while the number of osteoclasts between the treatment and control groups had no significant difference (p = 0.228). This study concludes that katuk leaves extract has effectiveness in increasing the number of osteoblasts in orthodontic treatment, while the decrease in osteoclasts is not statistically proven.

Protein Markers in Osteoporosis

: Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue. Biomarkers of bone turnover have been used for years in bone disease management, especially to determine response to treatment. They are substances found in biological fluids, produced during the bone remodelling process. Recently, new approaches for the detection of bone physiology and pathology biomarkers have been proposed, among which proteomics, with particular interest in osteoporosis. The objective of this manuscript is to review current knowledge on proteomics applied to osteoporosis in vivo. The analysis of the 14 studies published to date showed a range of proteins whose expression is altered in patients with osteoporosis. The relatively small number of papers depends mainly on high costs and technical limitations; due to the difficulty to collect osteoclasts, most of the studies performed proteomics on peripheral blood monocytes (PBMs), already accepted as an excellent osteoporosis cell model in vivo. Among the identified proteins, the most promising are represented by Gelsolin (GSN), Annexin A2 (ANXA2), and Prolyl 4-hydroxylase (P4HB). They have been related to bone mineral density (BMD), sometimes in apparent disagreement (some upregulated and others downregulated in patients with low BMD). : Finally, worthy of mention is the application of proteomics in the emerging field of microvesicles (MVs); they are important messengers, widely present in body fluids, and have recently emerged as novel targets for the diagnosis of multiple diseases, among which musculoskeletal diseases. In conclusion, the proteomic field is relatively novel in osteoporosis and has a considerable but theoretical potential; further investigations are needed in order to make proteome-derived markers applicable to clinical practice.

MicroRNA-548-3p overexpression inhibits proliferation, migration and invasion in osteoblast-like cells by targeting STAT1 and MAFB

Osteoporosis is the most common bone disease and a public health issue with increasing prevalence in Mexico. This disease is caused by an imbalance in the bone remodelling process mediated by osteoclast and osteoblast. MicroRNAs have emerged as key players during the differentiation of both types of cells specialized involved in bone metabolism. We found high expression levels of miR-548x-3p in circulating monocytes derived from postmenopausal osteoporotic women. This study aimed to analyse the functional characterization of miR-548x-3p roles in the bone remodelling process. We validated by RT-qPCR, the elevated levels of miR-548x-3p in circulating monocytes derived from osteoporosis women. Through bioinformatics analysis, we identify MAFB and STAT1 as potential target genes for miR-548x-3p. Both genes showed low levels of expression in circulating monocytes derived from osteoporotic women. In addition, we demonstrated the binding of miR-548x-3p to the 3′-UTR of both mRNAs. MiR-548x-3p was overexpressed in osteoblasts-like cell lines decreasing the levels of MAFB and STAT1 mRNA and protein. We found that miR-548x-3p overexpression inhibits the proliferation, migration and invasion of the cell lines evaluated. Our results identified, by the first time, the potential role of miR-548x-3p as a modulator of the bone remodelling process by regulating the expression of MAFB and STAT1.

Polyphenol-Rich Foods and Osteoporosis

Background: Osteoporosis is a metabolic disease affecting the bone mineral density and thus compromise the strength of the bones. Disease prevention through diet is the objective of the study and discussion. Among the several nutrients investigated, the intake of phenols seems to influence bone mineral density by acting as free radical scavengers, preventing oxidation-induced damage to bone cells. In addition, the growing understanding of the bone remodelling process supports the theory that inflammation significantly contributes to the etiopathogenesis of osteoporosis. Methods: To provide an overview of current evidence on polyphenol-rich foods and osteoporosis prevention we made a comprehensive review of the literature focusing on the state of art of the topic. Results: Some polyphenol-rich foods, including olive oil, fruit and vegetable, tea and soy, seem to be beneficial for preventing osteoporosis disease and its progression. The mechanism is still partly unknown and may involve different pathways which include inflammation and other disease reactions. Conclusion: However, further research is needed to better understand the mechanisms regulating the molecular interaction between osteoporosis incidence and progression and polyphenol-rich foods. The current evidence suggests that dietary intervention with polyphenol rich foods may be useful to prevent incidence and progression of this condition.

The Effects of Tocotrienol on Bone Peptides in a Rat Model of Osteoporosis Induced by Metabolic Syndrome: The Possible Communication between Bone Cells

A positive association between metabolic syndrome (MetS) and osteoporosis has been demonstrated in previous animal studies. The mechanisms of MetS in orchestrating the bone remodelling process have traditionally focused on the interactions between mature osteoblasts and osteoclasts, while the role of osteocytes is unexplored. Our earlier studies demonstrated the bone-promoting effects of tocotrienol using a rat model of osteoporosis induced by MetS. This study aimed to investigate the expression of osteocyte-derived peptides in the bone of rats with MetS-induced osteoporosis treated with tocotrienol. Age-matched male Wistar rats (12-week-old; n = 42) were divided into seven experimental groups. Two groups served as the baseline and normal group, respectively. The other five groups were fed with a high-carbohydrate high-fat (HCHF) diet to induce MetS. The five groups of HCHF animals were treated with tocopherol-stripped corn oil (vehicle), annatto tocotrienol (60 and 100 mg/kg), and palm tocotrienol (60 and 100 mg/kg) starting from week 8. At the end of the study, the rats were sacrificed and their right tibias were harvested. Protein was extracted from the metaphyseal region of the proximal right tibia and levels of bone peptides, including osteoprotegerin (OPG), soluble receptor activator of nuclear factor-kappa B ligand (sRANKL), sclerostin (SOST), Dickkopf-related protein 1 (DKK-1), fibroblast growth factor-23 (FGF-23), and parathyroid hormone (PTH), were measured. The vehicle-treated animals displayed higher levels of sRANKL, SOST, DKK-1, FGF-23, and PTH as compared to the normal animals. Oral supplementation of annatto and palm tocotrienol (60 and 100 mg/kg) reduced the levels of sRANKL and FGF-23 in the HCHF animals. Only 100 mg/kg annatto and palm tocotrienol lowered SOST and DKK-1 levels in the HCHF animals. In conclusion, tocotrienol exerts potential skeletal-promoting benefit by modulating the levels of osteocytes-derived bone-related peptides.

Clinical Efficacy of Bone Reconstruction Surgery with Frozen Cortical Bone Allografts for Nonunion of Radial and Ulnar Fractures in Toy Breed Dogs

Objective To evaluate the effectiveness of frozen cortical bone allografts (FCBA) in the treatment of severe radial and ulnar atrophic nonunion fractures. Animals Toy breed dogs with nonunion of radial and ulnar fractures (n = 15). Methods Severe atrophic nonunion fractures were treated with FCBA (eight infected and seven non-infected fractures). Radiographs obtained immediately after surgery, and 1, 2, 3, 6 and 12 months later were evaluated and scored for the periosteal reaction at the bone regeneration sites, the healing process in the bone connection areas at both the proximal and distal sites, and the bone remodelling process within the allografts. Results Improvements in the fracture-healing process and weight-bearing function were observed in all cases. Radiographic scores at the bone connection areas and within the allograft improved significantly over time (p < 0.05). There were not any significant differences in radiographic scores between the infected and non-infected groups. Clinical Significance Bone reconstruction with FCBA is effective in the treatment of radial and ulnar nonunion fractures associated with large bone defects, regardless of the infection status of the surgical site.

MECHANISMS IN ENDOCRINOLOGY: Genetics of human bone formation

Throughout life, bone is continuously remodelled to be able to fulfil its multiple functions. The importance of strictly regulating the bone remodelling process, which is defined by the sequential actions of osteoclasts and osteoblasts, is shown by a variety of disorders with abnormalities in bone mass and strength. The best known and most common example of such a disorder is osteoporosis, which is marked by a decreased bone mass and strength that consequently results in an increased fracture risk. As osteoporosis is a serious health problem, a large number of studies focus on elucidating the aetiology of the disease as well as on the identification of novel therapeutic targets for the treatment of osteoporotic patients. These studies have demonstrated that a large amount of variation in bone mass and strength is often influenced by genetic variation in genes encoding important regulators of bone homeostasis. Throughout the years, studies into the genetic causes of osteoporosis as well as several rare monogenic disorders with abnormal high or low bone mass and strength have largely increased the knowledge on regulatory pathways important for bone resorption and formation. This review gives an overview of genes and pathways that are important for the regulation of bone formation and that are identified through their involvement in monogenic and complex disorders with abnormal bone mass. Furthermore, novel bone-forming strategies for the treatment of osteoporosis that resulted from these discoveries, such as antibodies against sclerostin, are discussed as well.

Correlation between estrogen and alkaline phosphatase expression in osteoporotic rat model

Background: Osteoporosis is a systemic disease that can decrease bone density as a result of imbalance bone remodeling and bone resorption. Estrogen reduction due to menopause can increase osteoclast activity and furthermore decrease bone density. Estrogen can stimulate alkaline phosphatase (ALP) expression, collagen type I and osteocalcin in bone remodelling process. Ovariectomized rat is a common animal for studying patofisiology, diagnosis and treatment osteoporosis patient. Purpose: To evaluate correlation between estrogen and ALP expression in osteoporotic rat model mandible. Methode: 18 female wistar rats, 2 months old, 200 grams were divided into 2 groups, ovariectomized group and sham surgery as control group. Surgery was done under intra muskular anesthesia using combination 2% xylazine 1cc and 10% ketamine 1cc. After 12 weeks, mandible was taken for ALP examination and blood from heart was taken to evaluate the amount of estrogen. Result: There was significant correlation between estrogen and ALP expression in osteoporotic rat model mandible. Conclusion: The amount of estrogen can influence ALP expression activity.