Prevent Bone Loss Research Articles

A pulse survey: assessment and management of bone loss in spinal cord injury.

An online survey OBJECTIVES: To describe current clinical practices regarding osteoporosis assessment and management in people with Spinal Cord Injury (SCI) and compare them to recommended diagnostic tests and interventions. An international collaboration surveying professionals working in SCI Medicine. Online cross-sectional survey regarding clinical practice trends in the assessment and treatment of osteoporosis in people with SCI. Assessment of whether discrete professional characteristics influenced practices and if those practices were consistent with recommendations from professional organizations. Eighty-two professionals working in SCI Medicine completed the survey. Respondents were equally likely to test for bone loss during the post-acute phase (between 4- and 18-months post injury) and after low impact fracture (41.46% and 42.68%, respectively) and more likely to test during the chronic phase (51.22%). The majority of respondents (n = 56, 70%) assessed bone density with DXA at the hip, and many (48.78%, n = 40) prescribed simultaneous mobilization, vitamin D and calcium to prevent bone loss in the acute, post-acute and chronic phases. A number of evaluations and interventions were inconsistent with best practice recommendations. Given that reported practices for detection and treatment of osteoporosis in SCI are inconsistent and not data-driven, there is need for dissemination and adoption of existing clinical practice guidelines.

Therapeutic potential of annatto tocotrienol with self-emulsifying drug delivery system in a rat model of postmenopausal bone loss

Tocotrienol has been shown to prevent bone loss in animal models of postmenopausal osteoporosis, but the low oral bioavailability might limit its use. A self-emulsifying drug delivery system (SEDDS) could increase the bioavailability of tocotrienol. However, evidence of this system in improving the skeletal effects of tocotrienol is scanty. This study aims to evaluate the therapeutic efficacy of annatto tocotrienol with SEDDS in a rat model of postmenopausal bone loss. Ten-month-old female Sprague Dawley rats were randomized into six groups. The baseline group was euthanatized at the onset of the study. Four other groups underwent ovariectomy to induce estrogen deficiency. The sham underwent similar surgery procedure, but their ovaries were retained. Eight weeks after surgery, the ovariectomized rats received one of the four different regimens orally daily: (a) SEDDS, (b) annatto tocotrienol [60 mg/kg body weight (b.w.)] without SEDDS, (c) annatto-tocotrienol (60 mg/kg b.w.) with SEDDS, (d) raloxifene (1 mg/kg b.w.). After eight weeks of treatment, blood was collected for the measurement of delta-tocotrienol level and oxidative stress markers. The rats were euthanized and their bones were harvested for the evaluation of the bone microstructure, calcium content and strength. Circulating delta-tocotrienol level was significantly higher in rats receiving annatto tocotrienol with SEDDS compared to the group receiving unformulated annatto-tocotrienol (p < 0.05). Treatment with unformulated or SEDDS-formulated annatto tocotrienol improved cortical bone thickness, preserved bone calcium content, increased bone biomechanical strength and increased antioxidant enzyme activities compared with the ovariectomized group (p < 0.05). Only SEDDS-formulated annatto tocotrienol improved trabecular microstructure, bone stiffness and lowered malondialdehyde level (p < 0.05 vs the ovariectomized group). The improvement caused by annatto tocotrienol was comparable to raloxifene. In conclusion, SEDDS improves the bioavailability and skeletal therapeutic effects of annatto tocotrienol in a rat model of postmenopausal bone loss. This formulation should be tested in a human clinical trial to validate its efficacy.

Application of 3D Printing-Assisted Articulating Spacer in Two-Stage Revision Surgery for Periprosthetic Infection after Total Knee Arthroplasty: A Retrospective Observational Study.

Background Bone cement spacers are widely used in two-stage revision surgeries for periprosthetic joint infection (PJI) after total knee arthroplasty. Current spacer design results in insufficient release of drugs; therefore, current spacers have low efficacy. In this study, we explored a set of alternative articular spacer using 3D printing technology. This novel spacer will increase effectiveness of revision surgery for PJI. Methods The spacer was designed using CAD software and constructed on site using 3D-printed silicone mold during debridement surgery. We carried out a retrospective study among patients undergoing treatment using traditional static and new articular spacers. Infection control rate, bone loss, difficulty of revision surgery, knee joint range of motion, function evaluation, and subjective satisfaction of the patients in the two groups were compared. Results Forty-two patients undergoing knee revision surgery between Jan 2014 and Nov 2019 were included in this study. Twenty-two patients were treated with static antibiotic cement spacers, whereas the other twenty patients were with treated with 3D printing-assisted antibiotic loaded articulating spacers. Patients in the articular group showed significantly lower bone loss on the femur site and tibial site compared with patients in the static group. In addition, patients in the articular group showed significantly less operation time, intraoperative blood loss, and improved knee function and patient overall satisfaction compared with patients in the static group. Conclusions The 3D printing-assisted articular spacer provides satisfactory range of motion during the interim period, prevents bone loss, facilitates second-stage reimplantation and postoperative rehabilitation, and results in low reinfection and complication rates.

Promoting adherence to bone-loading exercises in postmenopausal women with low bone mass.

We recently completed a parent study (Bone Loading Exercises versus Risedronate on Bone Health in Post-menopausal Women [NIH# R01NR015029]) examining bone-loading exercises to prevent bone loss in postmenopausal women with low bone mass. Forty-three million US women have low bone mass and increased risk for fractures. Bone-loading exercises (weight-bearing and resistance training) can preserve bone mass and decrease risk of fractures. However, multiple barriers prevent women from exercising and adherence rates are low. This secondary analysis of the parent study (a) examined barriers specific to women participating in bone-loading exercises; (b) described effectiveness of self-efficacy strategies used in the parent study for increasing confidence in knowledge and reducing barriers; and (c) applied study findings and principles of self-efficacy and self-regulation in development of guidelines for promoting adherence to exercises. Seventy-two women were randomized to the exercise group and completed 12 months of exercises. Instruments for self-efficacy were completed at 2 weeks and barriers interference at 6 months. Percent adherence was measured as the number of exercise sessions attended divided by the number prescribed. In the 12-month study, average adherence to exercises was 58.9%. Lower adherers reported lack of self-regulation skills such as "lack of time" as the most frequent barriers to exercise. Guidelines developed included promotion of skills for self-regulation (such as regulation of time) as well as self-efficacy to improve adherence rates. Nurse practitioners may be the most motivated of all providers to use guidelines promoting exercise for women in their clinical practice.

Muscle-bone axis in children with chronic kidney disease: current knowledge and future perspectives.

Bone and muscle tissue are developed hand-in-hand during childhood and adolescence and interact through mechanical loads and biochemical pathways forming the musculoskeletal system. Chronic kidney disease (CKD) is widely considered as both a bone and muscle-weakening disease, eventually leading to frailty phenotype, with detrimental effects on overall morbidity. CKD also interferes in the biomechanical communication between two tissues. Pathogenetic mechanisms including systemic inflammation, anorexia, physical inactivity, vitamin D deficiency and secondary hyperparathyroidism, metabolic acidosis, impaired growth hormone/insulin growth factor 1 axis, insulin resistance, and activation of renin-angiotensin system are incriminated for longitudinal uncoordinated loss of bone mineral content, bone strength, muscle mass, and muscle strength, leading to mechanical impairment of the functional muscle-bone unit. At the same time, CKD may also interfere in the biochemical crosstalk between the two organs, through inhibiting or stimulating the expression of certain osteokines and myokines. This review focuses on presenting current knowledge, according to in vitro, in vivo, and clinical studies, concerning the pathogenetic pathways involved in the muscle-bone axis, and suggests approaches aimed at preventing bone loss and muscle wasting in the pediatric population. Novel therapeutic targets for preserving musculoskeletal health in the context of CKD are also discussed.

Asarylaldehyde enhances osteogenic differentiation of human periodontal ligament stem cells through the ERK/p38 MAPK signaling pathway

Periodontitis is an inflammatory disease that affects tooth-supporting tissues. Chronic inflammation can progress to periodontitis, which results in loss of alveolar bone. Asarylaldehyde is a potential substance for bone metabolism present in natural compounds. Here, we propose the application of asarylaldehyde in the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) to prevent bone loss. We investigated the effect of asarylaldehyde on hPDLSCs together with bone differentiation media in vitro. The osteogenic differentiation effect was observed after treatment of hPDLSCs with several concentrations of asarylaldehyde. After 21 days, osteogenic cells were identified by mineralization. We also observed that asarylaldehyde increased the mRNA expression of osteoblast-specific markers in hPDLSCs. Interestingly, asarylaldehyde regulated the levels of alkaline phosphatase (ALP) transcriptional activity through the p38/extracellular-signal-regulated kinase (ERK) signaling pathway. Notably, asarylaldehyde induced hPDLSCs to promote osteogenic differentiation. These results suggest that asarylaldehyde plays a key role in the osteogenic differentiation of hPDLSCs. Asarylaldehyde may be a good candidate for the application of natural compounds in future in periodontal regeneration.

Exendin-4 promotes bone formation in diabetic states via HDAC1-Wnt/β-catenin axis

Exendin-4 has been found to have hypoglycemic effect and prevent bone loss in diabetic patients, but its mechanism of preventing bone loss is still unclear. In this study, high-fat diet combined with streptozotocin was used to establish type 2 diabetes mellitus (T2DM) mice, and bone marrow mesenchyme stem cells (BMSCs) were isolated for osteogenic induction in vitro. Alizarin red staining and ALP activity detection were used to observe the effect of exendin-4 on osteogenic differentiation of BMSCs. Western blot was used to detect the proteins expression in BMSCs. In vivo, the effects of exendin-4 treatment on body weight, blood glucose, bone density and bone quality of T2DM mice were observed by treatment with exendin-4. The results showed that exendin-4 promoted osteogenic differentiation of T2DM derived BMSCs, down-regulated histone deacetylase 1 (HDAC1) and p-β-Catenin proteins expression, and up-regulated Wnt3, β-Catenin and runt-related transcription factor 2 (Runx 2) proteins expression. In vivo, exendin-4 effectively suppressed the blood glucose and increased body weight of T2DM mice, and significantly improved bone density and bone quality of the right tibia. Interestingly, by over-expression of HDAC1 in BMSCs, the effect of exendin-4 on promoting osteogenic differentiation of BMSCs was attenuated, and the regulation of Wnt3a, β-Catenin, p-β-Catenin or Runx2 proteins were reversed. By injecting adenovirus containing HDAC1 into the right tibia of mice, the effect of exendin-4 on bone density and bone quality of T2DM mice was significantly attenuated. All above results suggest that the HDAC1-Wnt/β-Catenin signal axis is involved in the anti-diabetic bone loss effect of exendin-4, and HDAC1 may be the target of exendin-4.

The Effect of MMP-2 Inhibitor 1 on Osteogenesis and Angiogenesis During Bone Regeneration.

Bone regeneration is a popular research focus around the world. Recent studies have suggested that the formation of a vascular network as well as intrinsic osteogenic ability is important for bone regeneration. Here, we show for the first time that matrix metalloproteinase (MMP) 2 inhibitor 1 (MMP2-I1) has a positive role in the osteogenesis of human bone marrow mesenchymal stem cells (hBMSCs) and angiogenesis of human vascular endothelial cells (HUVECs). MMP2-I1 activated the p38/mitogen-activated protein kinase signaling pathway to promote the osteogenesis of hBMSCs, and promoted the angiogenesis of HUVECs via the hypoxia-inducible factor-1α signaling pathway. We also found that MMP2-I1 enhanced bone formation using a rat tibial defect model and prevented bone loss using an ovariectomy-induced mouse model of osteoporosis. Data from the mouse model demonstrated that MMP2-I1 generated more type H vessels (CD31hiEmcnhi) when preventing bone loss. These results provide important insights into the regulatory effects of MMP2-I1 on bone regeneration.

Anthocyanins, Microbiome and Health Benefits in Aging.

The percentage of individuals over the age of 60 is projected to reach 22% by 2050; chronic diseases associated with aging can present challenges for these individuals. Anthocyanins and the gut microbiome have each been studied as independent influencers of health. Both these factors have shown to have a positive effect on cardiovascular and bone health in individuals, as well as on the prevention or treatment of certain forms of cancers. Anthocyanins have shown to modulate the composition of the gut microbiome and may have overlapping mechanisms in the prevention and treatment of cardiovascular disease, cancer, neurodegenerative disorders and aging-associated bone loss. These health outcomes are responsible for the hospitalization and deaths of millions of Americans every year and they cost the United States billions of dollars each year to maintain, prevent and treat. Alternative methods of treatment and prevention are desired since conventional methods (surgical and pharmacological methods, physical therapy, etc.) can be costly and have significant side effects; evidence suggests that anthocyanins and the gut microbiome may be potential avenues for this. This review evaluates the findings of existing literature on the role of anthocyanins and the gut microbiome on health and their potential as a natural therapeutic agent or a target organ to provide an alternative to the conventional methods of disease prevention and treatment.

Morroniside promotes the osteogenesis by activating PI3K/Akt/mTOR signaling.

Morroniside exerts a proosteogenic effect, which can prevent bone loss. However, the detailed mechanism underlying Morroniside-regulated bone formation is unclear. Morroniside can maintain cell homeostasis by promoting PI3K/Akt/mTOR signaling. The purpose of this study is to explore the significance of PI3K/Akt/mTOR signaling in Morroniside-regulated osteogenesis. The results showed that Morroniside promoted the activities of PI3K, Akt, and mTOR in osteoblast precursor MC3T3-E1. The differentiation of MC3T3-E1 to mature osteoblasts promoted by Morroniside can be reversed by the pharmacological inhibition of PI3K or mTOR. Importantly, in the presence of Morroniside, the osteoblast differentiation suppressed by PI3K inhibitor was reversed by mTOR overexpression. In vivo assays showed that in bone tissue of ovariectomized mice, Morroniside-enhanced osteoblast formation was reversed by the pharmacological inhibition of PI3K or mTOR. In conclusion, Morroniside can promote the osteogenesis through PI3K/Akt/mTOR signaling, which provides a novel clue for the strategy of Morroniside in treating osteoporosis.

Simulated effects of early menopausal bone mineral density preservation on long-term fracture risk: a feasibility study.

Preventing early menopausal bone loss may substantially reduce the future burden of osteoporosis. We modelled the effects of infrequent zoledronic acid infusions on long-term fracture risk. Data from the Canadian Multicentre Osteoporosis Study (CaMos) were used to determine the expected natural history of femoral neck areal bone mineral density (BMD) and fracture risk (using FRAX®) from ages 50-80 for women with no antiresorptive drug exposures. We modelled the effects of three infusions of zoledronic acid (at ages 50, 55, 60) on long-term fracture risk, assuming this intervention would preserve BMD until age 65 years, followed by losses mirroring early menopausal BMD loss. At age 65, untreated women and zoledronic acid recipients had expected mean (SD) femoral neck T-scores of - 1.5(1.0) and - 0.8(1.0), 10-year major osteoporotic fracture (MOF) risks of 9.8%(5.0) and 8.0%(3.7) and hip fracture risks of 1.7%(2.4) and 0.8%(1.2), respectively. At age 80, untreated women and zoledronic acid recipients had expected femoral neck T-scores of - 1.9(0.9) and - 1.4(0.9), MOF risks of 17.9%(8.2) and 14.9%(6.4) and hip fracture risks of 6.3%(6.2) and 4.4%(4.5), respectively. The expected proportion of women with femoral neck T-score ≤ - 2.5 was 14.9% for untreated women and 3.8% for zoledronic acid recipients at age 65, increasing to 28.1% and 12.0%, respectively, at age 80. Numbers-needed-to-treat to prevent one case of densitometric osteoporosis were 9 at age 65 and 5 at age 80. Infrequent infusions of zoledronic acid, initiated early in menopause, are expected to reduce long-term fracture risk and result in a substantial reduction in the proportion of women with densitometric osteoporosis after age 65.

Strontium-releasing sol–gel bioactive glass spheres and their ability to stimulate osteogenic differentiation in osteoporotic bone marrow mesenchymal stem cells

Osteoporosis is a metabolic disease that affects bone tissue and is highly associated with bone fractures. Due to the low bioavailability of conventional treatments for this disease, an alternative has been developed to project systems for the local release of therapeutic agents, such as bioactive glass (BG) containing therapeutic ions and molecules that are released during dissolution. In this study, submicron BG spheres derived from the sol–gel process containing Sr, a potential ion to prevent bone loss and increase bone formation, were evaluated. For the first time, the effect of these particles was investigated on the reduced osteogenic potential of bone marrow mesenchymal stem cells (BMMSCs) obtained from osteoporotic rats. The obtained submicron and spherical Sr-containing BG particles showed controlled ion release capacity, and osteogenic differentiation assays showed that these materials could stimulate the reduced differentiation potential of BMMSCs from osteoporotic rats due to Sr release.

Alveolar Preservation with Albumin and Gentamycin-Coated Allograft after Third Molar Tooth Removal: A Randomized Clinical Trial

Alveolar preservation can minimize bone resorption after tooth removal and additional topical antibiotics might also be considered. The goal of this study was to observe alveolar preservation with albumin and gentamycin-coated allograft compared to unfilled control sockets after mandibular third molar removal. Twenty-two patients were involved, 11 in the control group and 11 in the test group. CBCT analysis and micromorphometric analysis were performed. After one year, graft integration was observed with remaining graft particles. Micromorphometric analysis showed increased density and lower trabeculae formation in the grafted group. The buccal height reduction of the alveolar ridge was significantly lower when alveolar preservation was applied (control: 2.54 ± 2.01 mm, graft: 1.37 ± 1.04 mm, p &lt; 0.05). Horizontal bone loss prevention was not significant. At the distal site of the second molar, the marginal bone level (MBL) was significantly lower in the control group. At the control group, five pockets persisted from the eight initial and all healed in the graft group. Alveolar preservation improves bone formation, helps to preserve the buccal bone crest, and minimizes MBL loss and pocket formation on the adjacent teeth. Thus, it needs to be also considered after third molar surgical removal.

Intraperitoneal injection of Desferal\xae alleviated the age-related bone loss and senescence of bone marrow stromal cells in rats

BackgroundAge-related bone loss plays a vital role in the development of osteoporosis and osteoporotic fracture. Bone marrow stromal cell (BMSC) senescence is highly associated with osteoporosis and limits the application of BMSCs in regenerative medicine. Hypoxia is an essential component for maintaining the normal physiology of BMSCs. We have reported that activation of hypoxia-induced factor by deletion of von Hippel-Lindau gene in osteochondral progenitor cells protected mice from aging-induced bone loss. However, whether pharmacologically manipulation of hypoxic niche would attenuate age-related bone loss and dysfunction of BMSCs is not well understood.MethodsTwelve-month-old Sprague-Dawley rats were used as an aged model and were intraperitoneally injected with Desferal® (20, 60 mg/kg weight or vehicle), three times a week for a continuous 8-week period. Two-month-old young rats were set as a reference. After 8 weeks, micro-CT and HE staining were performed to determine the effect of Desferal® on bone loss. In order to investigate the effects of Desferal® on BMSC senescence, 12-month-old rats were treated with high-dose Desferal® (60 mg/kg weight) daily for 10 days. BMSCs were isolated and evaluated using CCK-8 assay, colony-forming cell assay, cell differentiation assay, laser confocal for reactive oxygen species (ROS) level, senescence-associated β-galactosidase (SA-β-gal) staining, and molecular expression test for stemness/senescence-associated genes.ResultsMicro-CT and HE staining showed that high-dose Desferal® significantly prevented bone loss in aged rats. Compared with vehicle group, the ex vivo experiments showed that short-term Desferal® administration could promote the potential of BMSC growth (proliferation and colony formation ability) and improve the rebalance of osteogenic and adipogenic differentiation, as well as rejuvenate senescent BMSCs (ROS level and SA-β-gal staining) and revise the expression of stemness/senescence-associated genes. The potential of BMSCs from 12M-H-Desferal® group at least partly revised to the level close to 2-month-old group.ConclusionsThe current study suggested that Desferal®, an iron-chelating agent, could alleviate age-related bone loss in middle-aged rats. Meanwhile, we found that short-term intraperitoneal injection of Desferal® partly rejuvenate BMSCs from aged rats. Overall, we demonstrated a novel role of Desferal® in rejuvenating aged BMSCs and preventing age-related bone loss.

Therapies for Preventing Bone Loss with Glucocorticoid Treatment.

We aim to critically review recent recommendations regarding preventative strategies for glucocorticoid-induced osteoporosis and provide a summary of key evidence regarding available interventions. Lifestyle optimization remains the hallmark of bone health preservation. Early initiation of anti-osteoporotic agents in the setting of glucocorticoid exposure is essential, guided by appropriate risk stratification. Recommendations for calcium and vitamin D intake optimization are well-supported across all risk strata. Bisphosphonates are the mainstay of pharmacological therapy. Newer agents such as denosumab and teriparatide have demonstrated comparative benefit in terms of incident fracture risk reduction and bone mineral density preservation, with comparable adverse events. With due consideration to cost, resource availability, and patient values and preferences, these agents may warrant use as the first-line agents in this setting. Glucocorticoid-induced osteoporosis remains preventable and warrants early and targeted evidence-based therapy.

Effect of alendronate on the femoral metaphyseal defect under carbamazepine in ovariectomized rats

BackgroundThe use of antiepileptic drugs and estrogen deficiency put forward higher requirements for bone defect regeneration. The present study investigated the effects of alendronate (ALN) on femoral bone defect in ovariectomized (OVX) rats under the influence of carbamazepine (CBZ).MethodsOne hundred female SD rats at 3 months of age were either sham-operated or OVX and divided into four groups: sham control (CON); OVX control (OVX); ovariectomized rats treated with CBZ via gavage (75 mg/kg/day; CBZ); ovariectomized rats treated with CBZ plus ALN (2 mg/kg/day; CBZ-ALN). A critical-sized femoral metaphyseal bone defect was established in all female SD rats. Animals from the CBZ and CBZ-ALN groups received drugs by gavage the day after bone defect surgery was performed. After the rats were sacrificed, the defected area located in the distal femur was harvested for evaluation by microcomputed tomography (micro-CT), hematoxylin and eosin (HE) staining, and Masson’s trichrome staining. The samples were also analyzed by biomechanics and immunohistochemical evaluation (IHC). Besides, biochemical analysis evaluates all serum samples.ResultsThe present study showed that ovariectomy changed the microstructural parameters of bone. The use of CBZ further decreased femur bone mass while treatment with ALN prevented bone loss. Compared to OVX and CBZ groups, CBZ-ALN group promoted bone neoformation and enhanced the ultimate load of the femur bone. However, the group of CBZ-ALN did not return to normal levels compared with the CON group. Besides, we noticed that CBZ-ALN group reduced tartrate-resistant acid phosphatase-5b (Tracp-5b) expression and had no significant effect on the expression of osteocalcin (OCN) and type I collagen (Col-I) in IHC compared with CBZ group. Biochemical analysis results presented that systemic delivery of CBZ showed pernicious effects on bone formation and resorption in ovariectomized rats, with the worse effects on C-terminal crosslinked telopeptide of type I collagen (CTX-1). Besides, a significant decrease in CTX-1 levels was observed in CBZ-ALN group as compared to the group of CBZ.ConclusionThese results demonstrated that ALN can effectively reverse the effects of CBZ on the microarchitectural properties of bone, and thus can have a positive effect on local bone neoformation in rats with osteoporosis.Clinical relevanceThe dose of 2 mg/kg ALN improves the negative effect of prescription of CBZ at 75 mg/kg and promotes bone neoformation of femoral bony deficits.

Tryptophan and Kynurenine Enhances the Stemness and Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stromal Cells In Vitro and In Vivo.

Aging tissues present a progressive decline in homeostasis and regenerative capacities, which has been associated with degenerative changes in tissue-specific stem cells and stem cell niches. We hypothesized that amino acids could regulate the stem cell phenotype and differentiation ability of human bone marrow-derived mesenchymal stromal cells (hBMSCs). Thus, we performed a screening of 22 standard amino acids and found that D-tryptophan (10 μM) increased the number of cells positive for the early stem cell marker SSEA-4, and the gene expression levels of OCT-4, NANOG, and SOX-2 in hBMSCs. Comparison between D- and L-tryptophan isomers showed that the latter presents a stronger effect in inducing the mRNA levels of Oct-4 and Nanog, and in increasing the osteogenic differentiation of hBMSCs. On the other hand, L-tryptophan suppressed adipogenesis. The migration and colony-forming ability of hBMSCs were also enhanced by L-tryptophan treatment. In vivo experiments delivering L-tryptophan (50 mg/kg/day) by intraperitoneal injections for three weeks confirmed that L-tryptophan significantly increased the percentage of cells positive for SSEA-4, mRNA levels of Nanog and Oct-4, and the migration and colony-forming ability of mouse BMSCs. L-kynurenine, a major metabolite of L-tryptophan, also induced similar effects of L-tryptophan in enhancing stemness and osteogenic differentiation of BMSCs in vitro and in vivo, possibly indicating the involvement of the kynurenine pathway as the downstream signaling of L-tryptophan. Finally, since BMSCs migrate to the wound healing site to promote bone healing, surgical defects of 1 mm in diameter were created in mouse femur to evaluate bone formation after two weeks of L-tryptophan or L-kynurenine injection. Both L-tryptophan and L-kynurenine accelerated bone healing compared to the PBS-injected control group. In summary, L-tryptophan enhanced the stemness and osteoblastic differentiation of BMSCs and may be used as an essential factor to maintain the stem cell properties and accelerate bone healing and/or prevent bone loss.

An Exopolysaccharide Produced by Bifidobacterium longum 35624® Inhibits Osteoclast Formation via a TLR2-Dependent Mechanism.

The probiotic Bifidobacterium longum subsp. longum 35624® (B. longum 35624®), with its surface exopolysaccharide (EPS624), has previously been demonstrated to induce immunoregulatory responses in the host and may, therefore, be a novel approach to prevent bone loss in inflammatory conditions such as post-menopausal osteoporosis (PMO). The aim of this study was to investigate the effect of EPS624 on osteoclast and osteoblast differentiation and to assess the potential of B. longum 35624® to prevent bone loss in vivo. In vitro cell assays were used to assess the impact of EPS624 on osteoclast and osteoblast differentiation. The potential of two probiotic B. longum 35624® strains, including an EPS-deficient strain, for preventing ovariectomy (Ovx)-induced bone loss was assessed in a murine model. EPS624 prevented osteoclast formation from murine bone marrow precursors under both normal and TNFα-induced inflammatory conditions and modestly increased mineralized matrix deposition in osteogenic cell cultures. However, in the presence of an anti-TLR2 blocking antibody, or in MyD88-/-osteoclast precursors, the inhibitory effect of EPS624 on osteoclast formation was diminished or completely prevented, respectively. Moreover, EPS624 induced IL-10 production in osteoclast precursors in a TLR2-dependent manner, although IL-10 was dispensable in the EPS624-mediated inhibition of osteoclast formation. In addition, EPS624-producing B. longum 35624® partially prevented bone loss in Ovx mice when administered by oral gavage. This study introduced EPS624 as a potential anti-resorptive therapy, although optimal in vivo delivery of the probiotic strain for treating low-grade inflammatory diseases such as PMO remains to be determined.

Selenium Nanoparticles by Moderating Oxidative Stress Promote Differentiation of Mesenchymal Stem Cells to Osteoblasts.

PurposeRedox homeostasis plays an important role in the osteogenic differentiation of human mesenchymal stem cells (hMSCs) for bone engineering. Oxidative stress (OS) is believed to induce osteoporosis by changing bone homeostasis. Selenium nanoparticles (SeNPs), an antioxidant with pleiotropic pharmacological activity, prevent bone loss. However, the molecular mechanism underlying the osteogenic activity during hMSC–SeNP interaction is unclear.MethodsThis study assessed the effects of different concentrations (25, 50, 100, and 300 ng/mL) of SeNPs on the cell viability and differentiation ability of human embryonic stem cell-derived hMSCs. In addition, we analyzed OS markers and their effect on mitogen-activated protein kinase (MAPK) and Forkhead box O3 (FOXO3) during osteogenesis.ResultsSeNPs increased the cell viability of hMSCs and induced their differentiation toward an osteogenic over an adipogenic lineage by enhancing osteogenic transcription and mineralization, while inhibiting Nile red staining and adipogenic gene expression. By preventing excessive reactive oxygen species accumulation, SeNPs increased antioxidant levels in hMSCs undergoing osteogenesis compared to untreated cells. In addition, SeNPs significantly upregulated the gene and protein expression of phosphorylated c-Jun N-terminal kinase (JNK) and FOXO3a, with no significant change in the expression levels of extracellular signal-related kinase (ERK) and p38 MAPK.ConclusionThe results approved that low concentrations of SeNPs might enhance the cell viability and osteogenic potential of hMSCs by moderating OS. Increased JNK and FOXO3a expression shows that SeNPs might enhance osteogenesis via activation of the JNK/FOXO3 pathway. In addition, SeNP co-supplementation might prevent bone loss by enhancing osteogenesis and, thus, can be an effective candidate for treating osteoporosis through cell-based therapy.

Direct and Indirect Effect of Honey as a Functional Food Against Metabolic Syndrome and Its Skeletal Complications.

Metabolic syndrome (MetS) refers to the simultaneous presence of hypertension, hyperglycemia, dyslipidemia and/or visceral obesity, which predisposes a person to cardiovascular diseases and diabetes. Evidence suggesting the presence of direct and indirect associations between MetS and osteoporosis is growing. Many studies have reported the beneficial effects of polyphenols in alleviating MetS in in vivo and in vitro models through their antioxidant and anti-inflammation actions. This review aims to summarize the effects of honey (based on unifloral and multi-floral nectar sources) on bone metabolism and each component of MetS. A literature search was performed using the PubMed and Scopus databases using specific search strings. Original studies related to components of MetS and bone, and the effects of honey on components of MetS and bone were included. Honey polyphenols could act synergistically in alleviating MetS by preventing oxidative damage and inflammation. Honey intake is shown to reduce blood glucose levels and prevent excessive weight gain. It also improves lipid metabolism by reducing total cholesterol, triglycerides and low-density lipoprotein, as well as increasing high-density lipoprotein. Honey can prevent bone loss by reducing the adverse effects of MetS on bone homeostasis, apart from its direct action on the skeletal system. In conclusion, honey supplementation could be integrated into the management of MetS and MetS-induced bone loss as a preventive and adjunct therapeutic agent.