Jintiange proteins promote osteogenesis and inhibit apoptosis of osteoblasts by enhancing autophagy via PI3K/AKT and ER stress pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Tiger bone, which had long been used in traditional Chinese medicine, had the action of removing wind and alleviating pain, strengthening the sinews and bones, and often used to treat bone impediment, and atrophic debility of bones in TCM clinical practice. As a substitute of natural bone tiger, artificial tiger bone Jintiange (JTG), has been approved by the State Food and Drug Administration of China for relief the symptom of osteoporosis, such as lumbago and back pain, lassitude in loin and legs, flaccidity and weakness legs, and walk with difficulty based on TCM theory. JTG has similar chemical profile to natural tiger bone, and contains mineral substance, peptides and proteins, and has been shown to protect bone loss in ovariectomized mice and exert the regulatory effects on osteoblast and osteoclast activities. But how the peptides and proteins in JTG modulate bone formation remains unclear. AIM: To investigate the stimulating effects of JTG proteins on osteogenesis and explore the possible underlying mechanisms. MATERIALS AND METHODS: JTG proteins were prepared from JTG Capsules by extracting calcium, phosphorus and other inorganic elements using SEP-PaktC18 desalting column. MC3T3-E1 cells were treated with JTG proteins to evaluate their effects and explore the underlying mechanisms. Osteoblast proliferation was detected by CCK-8 method. ALP activity was detected using a relevant assay kit, and bone mineralized nodules were stained with alizarin red-Tris-HCl solution. Cell apoptosis was analyzed by flow cytometry. Autophagy was observed by MDC staining, and autophagosomes were observed by TEM. Nuclear translocations of LC3 and CHOP were detected by immunofluorescence and observed under a laser confocal microscope. The expression of key proteins related to osteogenesis, apoptosis, autophagy and PI3K/AKT and ER stress pathways was analyzed by Western Blot analysis. RESULTS: JTG proteins improved osteogenesis as evidenced by the alteration of proliferation, differentiation and mineralization of MC3T3-E1 osteoblasts, inhibited their apoptosis, and enhanced autophagosome formation and autophagy. They also regulated the expression of key proteins of PI3K/AKT and ER stress pathways. In addition, PI3K/AKT and ER stress pathway inhibitors could reverse the regulatory effects of JTG proteins on osteogenesis, apoptosis, autophagy and PI3K/AKT and ER stress pathways. CONCLUSION: JTG proteins increased the osteogenesis and inhibited osteoblast apoptosis by enhancing autophagy via PI3K/AKT and ER stress signaling pathways.

Exosomal miRNAs from Prostate Cancer Impair Osteoblast Function in Mice.

Prostate cancer (PCa) is the most frequent malignancy in older men with a high propensity for bone metastases. Characteristically, PCa causes osteosclerotic lesions as a result of disrupted bone remodeling. Extracellular vesicles (EVs) participate in PCa progression by conditioning the pre-metastatic niche. However, how EVs mediate the cross-talk between PCa cells and osteoprogenitors in the bone microenvironment remains poorly understood. We found that EVs derived from murine PCa cell line RM1-BM increased metabolic activity, vitality, and cell proliferation of osteoblast precursors by >60%, while significantly impairing mineral deposition (-37%). The latter was further confirmed in two complementary in vivo models of ossification. Accordingly, gene and protein set enrichments of osteoprogenitors exposed to EVs displayed significant downregulation of osteogenic markers and upregulation of proinflammatory factors. Additionally, transcriptomic profiling of PCa-EVs revealed the abundance of three microRNAs, miR-26a-5p, miR-27a-3p, and miR-30e-5p involved in the suppression of BMP-2-induced osteogenesis in vivo, suggesting the critical role of these EV-derived miRNAs in PCa-mediated suppression of osteoblast activity. Taken together, our results indicate the importance of EV cargo in cancer-bone cross-talk in vitro and in vivo and suggest that exosomal miRNAs may contribute to the onset of osteosclerotic bone lesions in PCa.

Hyperbaric oxygen therapy improves age induced bone dyshomeostasis in non-obese and obese conditions.

AIMS: To investigate the effects of hyperbaric oxygen therapy (HBOT) on metabolic disturbance, aging and bone remodeling in D-galactose-induced aging rats with and without obesity by determining the metabolic parameters, aging and oxidative stress markers, bone turnover markers, bone microarchitecture, and bone biomechanical strength. MATERIALS AND METHODS: Male Wistar rats were fed either a normal diet (ND; n = 18) or a HFD (n = 12) for 22 weeks. At week 13, vehicle (0.9% NaCl) was injected into ND-fed rats (NDV; n = 6), while 150 mg/kg/day of D-galactose was injected into 12 ND-fed rats (NDD) and 12 HFD-fed rats (HFDD) for 10 weeks. At week 21, rats were treated with either sham (NDVS, NDDS, or HFDDS; n = 6/ group) or HBOT (NDDH, or HFDDH; n = 6/group) for 14 days. Rats were then euthanized. Blood samples, femora, and tibiae were collected. KEY FINDINGS: Both NDD and HFDD groups developed aging as indicated by increased AGE level, increased inflammation and oxidative stress as shown by raised serum TNF-α and MDA levels, impaired bone remodeling as indicated by an increase in levels of CTX-1, TRACP-5b, and impaired bone structure/strength, when compared with those of the NDVS group. HFD aggravated these indicators of bone dyshomeostasis in D-galactose-treated rats. HBOT restored bone remodeling and bone structure/strength in the NDD group, however HBOT ameliorated bone dyshomeostasis in the HFDD group. SIGNIFICANCE: HBOT is a potential intervention to decrease the risk of osteoporosis and bone fracture in aging with or without obesity.

Mineral and Bone Consequences of High Dose Denosumab Therapy to Treat an Aneurysmal Bone Cyst, a Child Case Report.

Aneurysmal bone cysts (ABCs) are rare benign pseudotumoral bone lesions with potential aggressive behavior due to the extensive destruction of surrounding bone. Traditionally, these tumors were treated with open surgery, but there is more and more a shift to less invasive procedures. In particular, treatment for spinal ABCs is generally unsatisfactory due to the risk of morbidity, neurological impairment and recurrence, and there is a need for innovative therapies. Denosumab has been reported as a useful treatment in giant cell tumors of bone (GCTB), so its efficacy has been tested also in other fibro-osseus lesions affecting children and adolescents, such as spinal aneurysmal bone cysts. The pediatric literature is limited to case reports and small series, all of which highlight the efficacy of this treatment on lesions growth and associated bone pain. Some of these reports have already reported well known side effects associated with denosumab, such as hypocalcemia at the beginning of the treatment, and rebound hypercalcemia at the discontinuation. The latter seems to be more frequent in children and adolescents than in adults, probably due to the higher baseline bone turnover in children. In addition, the use of denosumab in young patients could affect both bone modeling and remodeling, even if the consequences on the growing skeleton have not been reported in detail. Here we describe the case of a spinal ABC diagnosed in an 8-year old young boy which was not accessible to surgery but responded favorably to denosumab. Our aim is to describe the rapid changes in mineral and bone homeostasis in this patient, that required advice from the experts of the European Reference Network (ERN) for rare bone and endocrine diseases.

Electroactive Biomaterials and Systems for Cell Fate Determination and Tissue Regeneration: Design and Applications.

During natural tissue regeneration, tissue microenvironment and stem cell niche including cell-cell interaction, soluble factors, and extracellular matrix (ECM) provide a train of biochemical and biophysical cues for modulation of cell behaviors and tissue functions. Design of functional biomaterials to mimic the tissue/cell microenvironment have great potentials for tissue regeneration applications. Recently, electroactive biomaterials have drawn increasing attentions not only as scaffolds for cell adhesion and structural support, but also as modulators to regulate cell/tissue behaviors and function, especially for electrically excitable cells and tissues. More importantly, electrostimulation can further modulate a myriad of biological processes, from cell cycle, migration, proliferation and differentiation to neural conduction, muscle contraction, embryogenesis, and tissue regeneration. In this review, endogenous bioelectricity and piezoelectricity are introduced. Then, design rationale of electroactive biomaterials is discussed for imitating dynamic cell microenvironment, as well as their mediated electrostimulation and the applying pathways. Recent advances in electroactive biomaterials are systematically overviewed for modulation of stem cell fate and tissue regeneration, mainly including nerve regeneration, bone tissue engineering, and cardiac tissue engineering. Finally, the significance for simulating the native tissue microenvironment is emphasized and the open challenges and future perspectives of electroactive biomaterials are concluded.

Medicinal Mushrooms for Prevention and Therapy of Osteoporosis (Review).

Osteoporosis is an important public health challenge. Several medicinal mushrooms are able to improve bone stability by influencing different steps of bone formation, mineralization, or resorption. In nearly all investigations, the effects have been shown in vitro or in animal assays and only very few in clinical studies. Positive results exist for medicinal mushrooms of the genera Cordyceps/Ophiocordyceps, Ganoderma, Grifola, Lentinula, Phellinus, Pleurotus, Taiwanofungus, Trametes, and Wolfiporia. The results for Hericium are not consistent. This article critically reviews these investigations and describes challenges for the future.

Insight into the roles of melatonin in bone tissue and bone­related diseases (Review).

Bone­related diseases comprise a large group of common diseases, including fractures, osteoporosis and osteoarthritis (OA), which affect a large number of individuals, particularly the elderly. The progressive destruction and loss of alveolar bone caused by periodontitis is a specific type of bone loss, which has a high incidence and markedly reduces the quality of life of patients. With the existing methods of prevention and treatment, the incidence and mortality of bone­related diseases are still gradually increasing, creating a significant financial burden to societies worldwide. To prevent the occurrence of bone­related diseases, delay their progression or reverse the injuries they cause, new alternative or complementary treatments need to be developed. Melatonin exerts numerous physiological effects, including inducing anti­inflammatory and antioxidative functions, resetting circadian rhythms and promoting wound healing and tissue regeneration. Melatonin also participates in the health management of bone and cartilage. In the present review, the potential roles of melatonin in the pathogenesis and progression of bone injury, osteoporosis, OA and periodontitis are summarized. Furthermore, the high efficiency and diversity of the physiological regulatory effects of melatonin are highlighted and the potential benefits of the use of melatonin for the clinical prevention and treatment of bone­related diseases are discussed.

The "Fat but Fit" Paradigm and Bone Health in Young Adults: A Cluster Analysis.

The fat but fit paradox has suggested that obese individuals with good fitness levels have lower cardiometabolic risk compared to individuals with normal weight but lower fitness levels. This paradigm has not been explored in the context of bone health. The aim of this study was to test whether categories of fat but fit paradigm assessed by body fat percentage and handgrip strength holds up in young adults and to analyze the relationship between fat but fit categories and bone outcomes. Cluster cross-sectional analyses of data from 499 young adults aged 18 to 30 from Toledo and Cuenca, Spain were conducted. Body fat percentage, handgrip strength, bone mineral content (BMC), bone mineral density (BMD), and dietary nutrients such as, proteins, magnesium, calcium, phosphorus, potassium, and vitamin D were assessed. Cluster analysis of body fat percentage and handgrip z scores resulted in a classification of four clusters that could be interpreted according to Fat Unfit (FU), Unfat Unfit (UU), Fat Fit (FF) and Unfat Fit (UF) categories. ANCOVA models showed that young adults in clusters with higher handgrip strength levels (FF, UF) and with higher key bone nutrients levels (UF) had significantly higher total BMC values than their peers in the UU and FU cluster categories, after controlling for sex, age and height. This study provides two novel conclusions in relation to the fat but fit paradigm: first, it confirms the construct of the four clusters of body fat percentage and handgrip strength, and second, it reinforces the predictive validity of the fat but fit paradigm categories, indicating the positive effect, although it may not just be a causal relationship, of muscular strength and key bone nutrients on counteracting the negative effect of obesity on bone health.

Light-assisted therapy for biofilm infected micro-arc oxidation TiO2 coating on bone implants.

Implant-associated infections is a main factor leading to the failure of titanium (Ti) implants. Micro-arc oxidation is a convenient and effective technique to form a biocompatible metal (Ag+, Cu2+ and Zn2+) ions-doped TiO2 coatings to combat bacterial infections. However, compared with the sterilization by metal ions, light-triggered antibacterial therapies have accepted more attention due to its higher antibacterial efficiency and security. Although TiO2 is an excellent photocatalyst, it can be triggered by ultraviolet light due to the wide band gap. Herein, molybdenum disulfide (MoS2) modified TiO2 coating was fabricated on Ti by a hybrid process of micro-arc oxidation and hydrothermal treatment. The hybrid coating exhibits excellent antibacterial activity under the irradiation of 808 nm near-infrared light because of the synergistic antibacterial effects of reactive oxygen species and hyperthermia, and Staphylococcus aureus (S. aureus) biofilm can be eradicated within 15 min both in vivo and in vitro. Furthermore, collagen decorated on the surface of the hybrid coating can improve the proliferation, adhesion and spreading of MC3T3-E1 osteoblasts.

Therapeutic effect of pulsed electromagnetic field on bone wound healing in rats.

This study aimed to investigate the therapeutic effect of pulsed electromagnetic field (PEMF) on bone wound in rats as a potential therapy for bone fracture-related conditions. Male rats, aged 3 months, were used to construct model of bone wounding. Wound models were randomly selected to receive PEMF therapy at 1 to 10 mT intensity. Models that did not receive PEMF therapy were used as control. The serum concentrations of calcium (Ca), phosphorus (P) and alkaline phosphatase (ALP) were determined. Bone density and biomechanical properties of callus were measured using a tensile tester. Compared with control, rats subjected to PEMF therapy had similar weight gain, but significantly higher levels of serum Ca and ALP (P < .05) at 5 and 10 mT, while the serum level of P remained unchanged after PEMF therapy. The bone mineral density of callus increased after the therapy, particularly, after 5 and 10 mT therapy (P < .05). Biomechanical measurements showed that 21 days after the therapy, the maximum load, fracture load, elastic load and bending energy were significantly greater in rats receiving 5 and 10 mT PEMF therapy as compared with control (P < .05). Our experiments demonstrate that PEMF at 5 and 10 mT can significantly accelerate wound healing and enhance the repairing ability of bone tissue.

Silicon supplementation affects mineral metabolism but not bone density or strength in male broilers.

Because leg injuries produce welfare concerns and impact production for broilers, numerous interventions have been suggested as potential solutions. One mineral which may affect bone quality is silicon. The objective of this study was to determine if supplementing bioavailable silicon could affect bone morphology, mineralization, and strength without negatively influencing welfare and meat quality. Male broilers were raised from d 1 after hatching until 42 d of age and randomly assigned to treatment groups for silicon supplementation in water: Control (no supplement, C; n = 125), Normal (0.011 ml supplement/kg bodyweight, N; n = 125) and High (0.063 ml supplement/kg bodyweight, H; n = 125). Toe damage, footpad dermatitis, hock burn, and keel blisters were assessed on d 42. Blood samples were collected from wing veins for serum osteocalcin, pyridinoline cross-links, and mineral analysis. Clinical QCT scans and analysis were conducted immediately before four-point bending tests of tibias. Texture analysis was performed on cooked fillets. Silicon supplementation tended to increase daily water consumption in N and H as compared to C (P = 0.07). Footpad dermatitis and hock burn scores were higher in H than in N or C (P < 0.05 for both comparisons). Supplementation altered serum minerals (P < 0.001), but bone density, morphology, and strength measures were similar among groups. The highest level of supplementation in the current study on a kg bodyweight basis was above recommended intakes but below previous amounts demonstrating silicon's positive influence on bone, indicating that previously suggested minimum thresholds need to be reevaluated. Factors such as growth rate and mechanical loading likely play a greater role in developing bone quality than trying to supplement on top of good basic nutrition alone.

Vitamin D supplementation for term breastfed infants to prevent vitamin D deficiency and improve bone health.

BACKGROUND: Vitamin D deficiency is common worldwide, contributing to nutritional rickets and osteomalacia which have a major impact on health, growth, and development of infants, children and adolescents. Vitamin D levels are low in breast milk and exclusively breastfed infants are at risk of vitamin D insufficiency or deficiency. OBJECTIVES: To determine the effect of vitamin D supplementation given to infants, or lactating mothers, on vitamin D deficiency, bone density and growth in healthy term breastfed infants. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to 29 May 2020 supplemented by searches of clinical trials databases, conference proceedings, and citations. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs in breastfeeding mother-infant pairs comparing vitamin D supplementation given to infants or lactating mothers compared to placebo or no intervention, or sunlight, or that compare vitamin D supplementation of infants to supplementation of mothers. DATA COLLECTION AND ANALYSIS: Two review authors assessed trial eligibility and risk of bias and independently extracted data. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included 19 studies with 2837 mother-infant pairs assessing vitamin D given to infants (nine studies), to lactating mothers (eight studies), and to infants versus lactating mothers (six studies). No studies compared vitamin D given to infants versus periods of infant sun exposure. Vitamin D supplementation given to infants: vitamin D at 400 IU/day may increase 25-OH vitamin D levels (MD 22.63 nmol/L, 95% CI 17.05 to 28.21; participants = 334; studies = 6; low-certainty) and may reduce the incidence of vitamin D insufficiency (25-OH vitamin D < 50 nmol/L) (RR 0.57, 95% CI 0.41 to 0.80; participants = 274; studies = 4; low-certainty). However, there was insufficient evidence to determine if vitamin D given to the infant reduces the risk of vitamin D deficiency (25-OH vitamin D < 30 nmol/L) up till six months of age (RR 0.41, 95% CI 0.16 to 1.05; participants = 122; studies = 2), affects bone mineral content (BMC), or the incidence of biochemical or radiological rickets (all very-low certainty). We are uncertain about adverse effects including hypercalcaemia. There were no studies of higher doses of infant vitamin D (> 400 IU/day) compared to placebo. Vitamin D supplementation given to lactating mothers: vitamin D supplementation given to lactating mothers may increase infant 25-OH vitamin D levels (MD 24.60 nmol/L, 95% CI 21.59 to 27.60; participants = 597; studies = 7; low-certainty), may reduce the incidences of vitamin D insufficiency (RR 0.47, 95% CI 0.39 to 0.57; participants = 512; studies = 5; low-certainty), vitamin D deficiency (RR 0.15, 95% CI 0.09 to 0.24; participants = 512; studies = 5; low-certainty) and biochemical rickets (RR 0.06, 95% CI 0.01 to 0.44; participants = 229; studies = 2; low-certainty). The two studies that reported biochemical rickets used maternal dosages of oral D3 60,000 IU/day for 10 days and oral D3 60,000 IU postpartum and at 6, 10, and 14 weeks. However, infant BMC was not reported and there was insufficient evidence to determine if maternal supplementation has an effect on radiological rickets (RR 0.76, 95% CI 0.18 to 3.31; participants = 536; studies = 3; very low-certainty). All studies of maternal supplementation enrolled populations at high risk of vitamin D deficiency. We are uncertain of the effects of maternal supplementation on infant growth and adverse effects including hypercalcaemia. Vitamin D supplementation given to infants compared with supplementation given to lactating mothers: infant vitamin D supplementation compared to lactating mother supplementation may increase infant 25-OH vitamin D levels (MD 14.35 nmol/L, 95% CI 9.64 to 19.06; participants = 269; studies = 4; low-certainty). Infant vitamin D supplementation may reduce the incidence of vitamin D insufficiency (RR 0.61, 95% CI 0.40 to 0.94; participants = 334; studies = 4) and may reduce vitamin D deficiency (RR 0.35, 95% CI 0.17 to 0.72; participants = 334; studies = 4) but the evidence is very uncertain. Infant BMC and radiological rickets were not reported and there was insufficient evidence to determine if maternal supplementation has an effect on infant biochemical rickets. All studies enrolled patient populations at high risk of vitamin D deficiency. Studies compared an infant dose of vitamin D 400 IU/day with varying maternal vitamin D doses from 400 IU/day to > 4000 IU/day. We are uncertain about adverse effects including hypercalcaemia. AUTHORS' CONCLUSIONS: For breastfed infants, vitamin D supplementation 400 IU/day for up to six months increases 25-OH vitamin D levels and reduces vitamin D insufficiency, but there was insufficient evidence to assess its effect on vitamin D deficiency and bone health. For higher-risk infants who are breastfeeding, maternal vitamin D supplementation reduces vitamin D insufficiency and vitamin D deficiency, but there was insufficient evidence to determine an effect on bone health. In populations at higher risk of vitamin D deficiency, vitamin D supplementation of infants led to greater increases in infant 25-OH vitamin D levels, reductions in vitamin D insufficiency and vitamin D deficiency compared to supplementation of lactating mothers. However, the evidence is very uncertain for markers of bone health. Maternal higher dose supplementation (≥ 4000 IU/day) produced similar infant 25-OH vitamin D levels as infant supplementation of 400 IU/day. The certainty of evidence was graded as low to very low for all outcomes.

Optimizing DXA to Assess Skeletal Health: Key Concepts for Clinicians.

CONTEXT: The diagnosis of osteoporosis and assessment of fracture risk prior to a sentinel fracture was transformed by the widespread clinical use of dual-energy X-ray absorptiometry (DXA) for the assessment of bone mineral density (BMD). EVIDENCE ACQUISITION: This review is based on a collection of primary and review literature gathered from a PubMed search of "dual energy X-ray absorptiometry," "trabecular bone score," and "atypical femur fracture" among other keywords. PubMed searches were supplemented by the authors' prior knowledge of the subject. EVIDENCE SYNTHESIS: While uncertainty exists for some aspects of osteoporosis care, patient and clinician familiarity with BMD assessment for screening and monitoring is firmly established. Beyond BMD, lateral spine images obtained with DXA can diagnose osteoporosis and refine fracture risk through the detection of unrecognized vertebral fractures. In addition, analysis of DXA lumbar spine images can reflect changes in trabecular bone microarchitecture, a component of bone "quality" that predicts risk of fracture independent of BMD. Finally, monitoring of bone health by DXA may be extended to include assessment of the femoral cortices for rare but serious adverse effects associated with antiresorptive therapies. CONCLUSIONS: Increasing technologic sophistication requires additional consideration for how DXA imaging is performed, interpreted and applied to patient care. As with any test, clinicians must be familiar with DXA performance, pitfalls in analysis, and interpretation within each clinical context in which DXA is applied. With this perspective, care providers will be well positioned to contribute to continuous improvement of DXA performance and, in turn, quality of osteoporosis care.

Performance of parallel FDTD method for shared- and distributed-memory architectures: Application tobioelectromagnetics.

This work provides an in-depth computational performance study of the parallel finite-difference time-domain (FDTD) method. The parallelization is done at various levels including: shared- (OpenMP) and distributed- (MPI) memory paradigms and vectorization on three different architectures: Intel's Knights Landing, Skylake and ARM's Cavium ThunderX2. This study contributes to prove, in a systematic manner, the well-established claim within the Computational Electromagnetic community, that the main factor limiting FDTD performance, in realistic problems, is the memory bandwidth. Consequently a memory bandwidth threshold can be assessed depending on the problem size in order to attain optimal performance. Finally, the results of this study have been used to optimize the workload balancing of simulation of a bioelectromagnetic problem consisting in the exposure of a human model to a reverberation chamber-like environment.

Morphometric Effects of Whole-Body Vibration on the Bone in a Rat Model of Postmenopausal Osteoporosis.

OBJECTIVE: The purpose of this study was to analyze the morphometric effects of mechanical vibration with a duration of 4 or 8 weeks on the femur of oophorectomized Wistar rats. METHODS: Sixty-four female rats were submitted to oophorectomy or a sham operation, and each of those 2 groups were randomized into 4 groups: untreated and euthanized at week 12, untreated and euthanized at week 16, treated for 4 weeks and euthanized at week 12, and treated for 8 weeks and euthanized at week 16. The vibration treatment was performed for 10 min/d, with a frequency of 60 Hz, 3 d/wk. The rats were then euthanized and the right femur dissected. Subsequently, histomorphometric analysis was performed on the proximal epiphysis and diaphysis of the spongy and cortical bone, respectively. RESULTS: As expected, the oophorectomy groups presented reduction of spongy and cortical bone tissue. Further, the vibration therapy of 4 and 8 weeks' duration in the oophorectomized groups led to increased bone mass, observed as an increased percentage of spongy tissue, and increased thickness and percentage of cortical tissue. However, the variables of femoral neck diameter, mean area of the shaft, and number of osteocytes were not altered by oophorectomy and vibration. CONCLUSION: The mechanical vibration was effective in increasing the bone mass of the femur of oophorectomized Wistar rats, observed by increasing the percentage of spongy bone and increasing the percentage and thickness of cortical bone.

Vitamin K Nutrition and Bone Health.

Vitamin K is essential for blood coagulation and plays an important role in extrahepatic metabolism, such as in bone and blood vessels, and in energy metabolism. This review discusses the assessment of vitamin K sufficiency and the role of vitamin K in bone health. To elucidate the exact role of vitamin K in other organs, accurate tools for assessing vitamin K deficiency or insufficiency are crucial. Undercarboxylated vitamin K-dependent protein levels can be measured to evaluate tissue-specific vitamin K deficiency/insufficiency. Vitamin K has genomic action through steroid and xenobiotic receptor (SXR); however, the importance of this action requires further study. Recent studies have revealed that the bone-specific, vitamin K-dependent protein osteocalcin has a close relationship with energy metabolism through insulin sensitivity. Among the organs that produce vitamin K-dependent proteins, bone has attracted the most attention, as vitamin K deficiency has been consistently associated with bone fractures. Although vitamin K treatment addresses vitamin K deficiency and is believed to promote bone health, the corresponding findings on fracture risk reduction are conflicting. We also discuss the similarity of other vitamin supplementations on fracture risk. Future clinical studies are needed to further elucidate the effect of vitamin K on fracture risk.

Collagen Extract Derived from Yeonsan Ogye Chicken Increases Bone Microarchitecture by Suppressing the RANKL/OPG Ratio via the JNK Signaling Pathway.

Yeonsan Ogye is a traditional Korean chicken breed (Gallus domesticus, GD), with a dominant gene for fibromelanosis, showing entirely black fluffy head feathers, ear lobes, and pupils. GD collagen extract (78.6 g per 100 g total protein) was derived from the flesh of Yeonsan Ogye. The effects of GD collagen on bone mass, microarchitecture, osteogenic, osteoclastogenic differentiations, and function factor expression were investigated in ovariectomized (OVX) rats. GD collagen stimulated osteogenesis in OVX rats and increased tibial bone strength and calcium content. Micro-computed tomography analysis of tibia cross-sections revealed that GD collagen attenuated the OVX-induced changes in trabecular thickness, spacing, and number. GD collagen stimulated alkaline phosphatase activity, bone-specific matrix proteins (alkaline phosphatase (ALP), osteocalcin, collagen type I (COL-I)) and mineralization by activating bone morphogenetic protein 2 (BMP-2)/mothers against decapentaplegic homolog 5 (SMAD5)/runt-related transcription factor 2 (Runx2). GD collagen inhibited osteoclast differentiation and function gene markers (TRAP, cathepsin K) by interfering with the Wnt signaling, increasing OPG production, and reducing the expression of RANKL, TRAP, and cathepsin K. GD collagen promoted osteogenesis by activating the p38 signal pathway and prevented osteoclastogenesis by lowering the RANKL/OPG ratio and blocking the JNK signaling pathway. Dietary supplementation with GD collagen might inhibit osteoclastogenesis, stimulate osteoblastogenesis, and regulate bone metabolism.

The earliest domestic cat on the Silk Road.

We present the earliest evidence for domestic cat (Felis catus L., 1758) from Kazakhstan, found as a well preserved skeleton with extensive osteological pathologies dating to 775-940 cal CE from the early medieval city of Dzhankent, Kazakhstan. This urban settlement was located on the intersection of the northern Silk Road route which linked the cities of Khorezm in the south to the trading settlements in the Volga region to the north and was known in the tenth century CE as the capital of the nomad Oghuz. The presence of this domestic cat, presented here as an osteobiography using a combination of zooarchaeological, genetic, and isotopic data, provides proxy evidence for a fundamental shift in the nature of human-animal relationships within a previously pastoral region. This illustrates the broader social, cultural, and economic changes occurring within the context of rapid urbanisation during the early medieval period along the Silk Road.

Potential Application of Protamine for Antimicrobial Biomaterials in Bone Tissue Engineering.

Bacterial infection of biomaterials is a serious problem in the field of medical devices. It is urgently necessary to develop new biomaterials with bactericidal activity. Antimicrobial peptides and proteins (AMPs), alternative antibacterial agents, are expected to overcome the bacterial resistance. The aim of this study was to develop a new intelligent material in bone tissue engineering based on protamine-loaded hydroxyapatite (protamine/HAp) that uses AMPs rather than antibiotics. It was found that the adsorption of protamine to HAp followed the Langmuir adsorption model and was due to electrostatic and/or hydrophobic interactions. In vitro bacterial adhesion and growth on protamine/HAp was inhibited in a protamine dose-dependent manner. Adherent bacteria exhibited an aberrant morphology for high dosages of protamine/HAp, resulting in the formation of large aggregates and disintegration of the membrane. The released protamine from protamine/HAp also prevented the growth of planktonic bacteria in vitro. However, a high dosage of protamine from powders at loading concentrations over 1000 µg·mL-1 induced a cytotoxic effect in vitro, although those exhibited no apparent cytotoxicity in vivo. These data revealed that protamine/HAp (less than 1000 µg·mL-1) had both antimicrobial activity and biocompatibility and can be applied for bone substitutes in orthopedic fields.

Pivotal role of boron supplementation on bone health: A narrative review.

BACKGROUND: Boron is a trace element that plays an important role in numerous biological functions, including calcium metabolism, growth and maintenance of bone tissue. However, there are still no precise indications regarding a possible role of boron supplementation, and its amount of supplementation, to maintain bone health. So the aim of this narrative review was to consider the state of the art on the effectiveness of boron supplementation (alone or with other micronutrients) on growth and maintenance of bone in humans through control of calcium, vitamin D and sex steroid hormone metabolism in order to suggest a daily dosage of boron supplementation. MAIN FINDINGS: This review included 11 eligible studies: 7 regarding the supplementation with boron alone and 4 regarding supplementation with boron and other nutrients. Despite the number of studies considered being low, the number of subjects studied is high (594) and the results are interesting. CONCLUSIONS: The studies considered in this narrative review have evaluated the positive effectiveness on bone, in humans, through control of calcium, vitamin D and sex steroid hormone metabolism, considering a dietary supplementation of 3 mg/day of boron (alone or with other nutrients); this supplementation is demonstrably useful to support bone health (in order to prevent and maintain adequate bone mineral density), also considering the daily dose of 3 mg is much lower than the Upper Level indicated by EFSA in the daily dose of 10 mg.