Magnesium, parathyroid hormone and osteocalcin in the sera of hospitalized patients with chronic alcoholism

Levels of parathyroid hormone (PTH) and osteocalcin in hypomagnesemic sera of chronic alcoholism patients were carried out to evaluate the roles of chronic alcohol poisoning on bone metabolism. Serum gamma-GTP activity showed inverse relationships among serum Mg and osteocalcin in these patients and PTH levels were also more decreased in these patients than in healthy subjects. These results indicated that the direct actions of alcohol might be brought about by the deterioration of bone metabolism, due to the decrease of serum PTH and osteocalcin levels by chronic alcohol poisoning.     

Methionine synthase reductase polymorphisms are associated with serum osteocalcin levels in postmenopausal women

Homocysteine (Hcy) is thought to play an important role in the development of osteoporosis and fracture. Methionine synthase reductase (MTRR) is an enzyme involved in the conversion of Hcy to methionine. We hypothesized that certain genetic polymorphisms of MTRR leading to reduced enzyme activity may cause hyperhomocysteinemia and affect bone metabolism. We therefore examined the associations of the A66G and C524T polymorphisms of the MTRR gene with bone mineral density (BMD) and serum osteocalcin levels in postmenopausal women. Although we did not detect any significant associations between MTRR polymorphisms and BMD or serum osteocalcin levels, we found that the 66G/524C haplotype, which has reduced enzyme activity, was significantly associated with serum osteocalcin levels in a gene-dose dependent manner (P = 0.002). That is, the highest osteocalcin levels (34.5 +/- 16.8 ng/ml) were observed in subjects bearing two copies, intermediate osteocalcin levels (32.6 +/- 14.4 ng/ml) were observed in subjects bearing one copy, and the lowest levels of osteocalcin (28.8 +/- 10.9 ng/ml) were observed in subjects bearing no copies. These results suggest that the 66G/524C haplotype of the MTRR gene affect bone turn over rate.     

Euodia sutchuenensis Dode extract stimulates osteoblast differentiation via Wnt/β-catenin pathway activation

The Wnt/β-catenin pathway has a role in osteoblast differentiation and bone formation. We screened 100 plant extracts and identified an extract from Euodia sutchuenensis Dode (ESD) leaf and young branch as an effective activator of the Wnt/β-catenin pathway. ESD extract increased β-catenin levels and β-catenin nuclear accumulation in murine primary osteoblasts. The ESD extract also increased mRNA levels of osteoblast markers, including RUNX2, BMP2 and COL1A1, and enhanced alkaline phosphatase (ALP) activity in murine primary osteoblasts. Both ESD extract-induced β-catenin increment and ALP activation were abolished by β-catenin knockdown, confirming that the Wnt/β-catenin pathway functions in osteoblast differentiation. ESD extract enhanced terminal osteoblast differentiation as shown by staining with Alizarin Red S and significantly increased murine calvarial bone thickness. This study shows that ESD extract stimulates osteoblast differentiation via the Wnt/β-catenin pathway and enhances murine calvarial bone formation ex vivo.     

Markers of bone pain in hemodialysis patients with renal insufficiency

The patients receiving maintenance hemodialysis were divided into two groups in the absence and the presence of bone pain and investigated the markers of bone pain in these patients. These results suggested that the duration of receiving hemodialysis, serum concentrations of alkaline phosphatase, osteocalcin and parathyroid hormone became to be the markers of bone pain.     

Two-dimensional polyacrylamide gel electrophoresis reveals differences between osteoblast and fibroblast extracellular proteins.

Normal human skin fibroblast primary cell lines secrete over 50 proteins into culture medium. These have been mapped previously using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and this technique has now been used to investigate extracellular protein secretion by human osteoblasts in vitro. We report the mapping of a number of consistent markers specific to the osteoblast. In particular, one protein chain with posttranslational modifications was found to be unique to the osteoblast extracellular protein map. The absence of the N- and O-glycoforms of collagenase from the osteoblast profile in this study concurs with findings reported using the immunoprecipitation functional assay and Northern blot analysis. The use of 2-D PAGE in phenotypic assessment provides a more complete analysis than the standard range of single-parameter tests for osteoblasts. Mapping of extracellular and cellular proteins in addition to bone matrix protein analysis will allow a comprehensive analysis of normal osteoblast function. This technique may also be applied to the study of osteoblasts in relation to bone disease and in assessing the phenotypic shift within a normal osteoblast culture.     

New phosphorylated derivatives of carboxymethylcellulose with osteogenic activity

New phosphorylated derivatives of carboxymethylcellulose (CMC) and amidic CMC were realized using trisodium trimetaphosphate (STMP) as the phosphating agent. The new polysaccharides were characterized by infrared spectroscopy and elemental analysis. The characterized polysaccharides were then crosslinked and their rheological and swelling properties determined. The presence of phosphate groups made the three‐dimensional structures more compact and harder than the corresponding non‐phosphated hydrogels. Evaluation of the bioactivity of phosphorylated hydrogels toward osteoblast‐like cells (MG63) showed a significant increase in the osteocalcin production. Copyright © 2008 John Wiley & Sons, Ltd.     

Osteoblast cell membrane chromatography coupled with liquid chromatography and time‐of‐flight mass spectrometry for screening specific active components from traditional Chinese medicines

A method using osteoblast membrane chromatography coupled with liquid chromatography and time‐of‐flight mass spectrometry was developed to recognize and identify the specific active components from traditional Chinese medicines. Primary rat osteoblasts were used for the preparation of the stationary phase in the cell chromatography method. Retention components from the cell chromatography were collected and analyzed by liquid chromatography with time‐of‐flight mass spectrometry. This method was applied in screening active components from extracts of four traditional Chinese medicines. In total, 24 potentially active components with different structures were retained by osteoblast cell chromatography. There were five phenolic glucosides and one triterpenoid saponin from Curculigo orchioides Gaertn, two organic acids and ten flavonoids from Epimedium sagittatum Maxim, one phthalide compound and one organic acid from Angelica sinensis Diels, and two flavonoids and two saponins from Anemarrhena asphodeloides Bunge. Among those, four components (icariin, curculigoside, ferulaic acid, and timosaponin BII) were used for in vitro pharmacodynamics validation. They significantly increased the osteoblast proliferation, alkaline phosphatase activity, levels of bone gla protein and collagen type 1, and promoted mineralized nodule formation. The developed method was an effective screening method for finding active components from complex medicines that act on bone diseases.     

Immunoradiometric assay for prolactin in serum and tissue--comparison with radioimmunoassay

Prolactin (PRL) concentrations in sera and tumors of patients with various pituitary tumors were measured by both immunoradiometric assay (IRMA) and radioimmunoassay (RIA). PRL concentrations in sera and tumor tissues measured by IRMA were well correlated with those measured by RIA. PRL concentrations in sera reflected those of tumors removed. This IRMA is a simple and useful method for PRL determination in serum and tissue.     

In Vitro Osteoblast Differentiation is Negatively Regulated by Hoxc8

Hoxc8 has multiple roles in normal skeletal development. In this paper, a MC3T3-E1 subclone 4 osteogenic cell differentiation model was used to examine expression of Hoxc8 at multiple stages of osteogenesis. We found that Hoxc8 expression levels do not change in the early stage but increase in the middle stage and decrease in the late stage of osteogenesis. A knockdown of Hoxc8 by small-interfering RNA transfection in C2C12 cells indicated that Hoxc8 is a negative regulator of osteogenesis. Similarly, expression of Hoxc8 in C2C12 cells decreases alkaline phosphatase levels induced by bone morphogenetic protein-2 (BMP-2). The results of this study showed that Hoxc8 is involved in BMP-2-induced osteogenesis, and osteoblast differentiation in vitro is negatively regulated by Hoxc8, suggesting that Hoxc8 regulation is essential for osteoblast differentiation.     

Osteoblast culture on bioerodible polymers: studies of initial cell adhesion and spread

The development of systems for the growth of osteoblasts on bioerodible polymeric matrices was explored. Three classes of bioerodible polymers were studied as possible matrix supports for osteoblast growth: the poly(anhydrides), poly(phosphazenes) and poly(lactic acid/glycolic acid) copolymers. Neonatal calvarial cells from Sprague–Dawley rats were seeded onto polymer disks at a density of 1 × 10⁴ cells/cm². Initial attachment and spreading, rate of growth and morphology were determined, and retention of osteoblast-like phenotype was assessed through measurements of alkaline phosphatase activity in the presence and absence of 1,25(OH)₂ vitamin D3. All results were considered relative to tissue culture polystyrene. Cells were found to attach to all polymers at 8 hr post-seeding. By 24 hr, cell numbers on all polymers were found to be decreased, except for poly(lactic acid/glycolic acid). Rat calvarial osteoblasts seeded on poly-(lactic acid/glycolic acid) reached confluency and retained their phenotype. Successful construction of viable osteoblast–bioerodible polymer composite materials, as presented in our study, may find their usefulness as grafts for atrophic non-unions of bone, for healing craniofacial and other defects and for use as prosthetic implants or coatings. Composite systems of osteoblast cultures may also find their usefulness in furthering our understanding of bone differentiation, maturation and metabolism in a matrix environment.     

Enhanced effects of nano-scale topography on the bioactivity and osteoblast behaviors of micron rough ZrO2 coatings

Implant surface topography is one of the most important factors affecting the rate and extent of osseointegration. Randomly micron-roughened surfaces have been documented to support osteoblast adhesion, differentiation, and mineralized phenotype, and thus favoring bone fixation of implants to host tissues. However, few studies have been done yet to investigate whether their effects on osteoblast behaviors can be enhanced by incorporation of nano-scale topographic cues. To validate this hypothesis, zirconia coatings with micron roughness (about 6.6 μm) superimposed by nano-sized grains (<50 nm) were fabricated by plasma spraying. To validate the impact of nano-sized grains, post-treatments of surface polishing (SP) and heat treatment (HT) were performed on the as-sprayed (AS) coatings to change the surface topographies but keep the chemical and phase composition similar. Results of in vitro bioactivity test showed that apatite was formed only on coating surfaces with nano-sized grains (AS coatings), indicating the significance of nano-topographic cues on the in vitro bioactivity. Enhanced osteoblast adhesion and higher cell proliferation rate were observed on coatings with both micron-roughness and nano-sized grains (AS-coatings), compared to coatings with smooth surfaces (SP-coatings) and coatings with only micron-scale roughness (heat-treated coatings), indicating the significant effects of nano-size grains on osteoblast responses. As the micron rough surfaces have been well-documented to enhance bone fixation, results of this work suggest that a combination of surface modifications at both micron and nano-scale is required for enhanced osseointegration of orthopedic implants.     

X线平片、CT及MRI对四肢原发性骨肿瘤诊断效能比较

本文比较了X线平片、CT及MRI对四肢原发性骨肿瘤的诊断效能。回顾性收集了2012年1月到2018年12月期间入我院治疗的92例四肢原发性骨肿瘤患者的临床资料,比较了各病理类型四肢骨肿瘤发病部位、影像学检查特征和3种影像学检查方法判断良恶性肿瘤的效能。结果显示,92例患者中原发性骨肿瘤发生在肱骨为9.78%（9/92）,尺、桡骨为7.61%（7/92）,手骨为5.43%（5/92）,肩胛、锁骨为2.17%（2/92）,股骨为38.04%（35/92）,胫、腓骨为17.39%（16/92）,足骨为5.43%（5/92）,髋骨为14.13%（13/92）;X线对骨质增生/硬化和骨膜反应成像较佳,分别占85.87%和57.61%;CT对骨质增生/硬化、软组织肿块和骨膜反应成像较佳,分别占92.39%、66.30%、85.87%;MRI对软组织肿块、骨质增生/硬化、骨膜反应、骨髓水肿成像均较佳,分别占94.57%、82.61%、64.13%、22.83%。92例四肢骨肿瘤中,X线诊断恶性肿瘤的灵敏度为94.57%,均低于CT、MRI诊断的灵敏度（依次为95.65%、97.83%）,特异度82.14%,低于CT和MRI的89.29%,而MRI的阳性预测值、阴性预测值和准确率最高,分别为97.83%、89.29%、95.83%。X线、CT的ROC曲线下面积分别为0.767、0.855,均低于MRI的ROC曲线下面积0.942。本文发现X线片、CT、MRI对四肢原发性骨肿瘤的诊断各有优势,尽管MRI检查敏感性、特异性、准确性较高,但是将三者有效结合起来,可以更好地定位定性诊断,避免出现漏诊误诊。     

The Skeletal Effects of Tanshinones: A Review

Background: Osteoporosis results from excessive bone resorption and reduced bone formation, triggered by sex hormone deficiency, oxidative stress and inflammation. Tanshinones are a class of lipophilic phenanthrene compounds found in the roots of Salvia miltiorrhiza with antioxidant and anti-inflammatory activities, which contribute to its anti-osteoporosis effects. This systematic review aims to provide an overview of the skeletal beneficial effects of tanshinones. Methods: A systematic literature search was conducted in January 2021 using Pubmed, Scopus and Web of Science from the inception of these databases. Original studies reporting the effects of tanshinones on bone through cell cultures, animal models and human clinical trials were considered. Results: The literature search found 158 unique articles on this topic, but only 20 articles met the inclusion criteria and were included in this review. The available evidence showed that tanshinones promoted osteoblastogenesis and bone formation while reducing osteoclastogenesis and bone resorption. Conclusions: Tanshinones modulates bone remodelling by inhibiting osteoclastogenesis and osteoblast apoptosis and stimulating osteoblastogenesis. Therefore, it might complement existing strategies to prevent bone loss.     

新型介孔羟基磷灰石/壳聚糖-万古霉素药物释放系统复合材料的制备及体外抗菌和成骨能力

采用冷冻干燥法合成了介孔羟基磷灰石(HA)/壳聚糖(CS)-万古霉素(VCM)药物释放系统复合材料, 利用SEM, XRD和FTIR等方法对材料进行了表征. 结果证实CS与HA混合复合材料具有良好的孔径和孔隙率, 万古霉素吸附于复合材料的表面和内部. 细胞毒性实验[噻唑蓝(MTT)比色法]结果表明, 材料可以促进成骨细胞增殖且具有良好的细胞相容性. 体外抑菌实验结果证实此材料可长时间抑制耐甲氧西林金葡菌(MRSA)的生长, 具有良好的抑菌和杀菌能力. 细胞黏附实验结果表明, 成骨细胞附着于材料表面增殖并通过孔道延伸. 实时聚合酶链式反应(RT-PCR)实验结果表明, 在成骨相关标志产物胶原蛋白-1(COL-1)及骨形态发生蛋白-2(BMP-2)基因上均有较高的表达, 表明材料在体外可以促进成骨细胞生长, 具有良好的成骨能力.     

Precisely Controlled Delivery of Abaloparatide through Injectable Hydrogel to Promote Bone Regeneration

Side‐effects from allograft, limited bone stock, and site morbidity from autograft are the major challenges to traditional bone defect treatments. With the advance of tissue engineering, hydrogel injection therapy is introduced as an alternative treatment. Therapeutic drugs and growth factors can be carried by hydrogels and delivered to patients. Abaloparatide, as an analog of human recombinant parathyroid hormone protein (PTHrp) and an alternative to teriparatide, has been considered as a drug for treating postmenopausal osteoporosis since 2017. Since only limited cases of receiving abaloparatide with polymeric scaffolds have been reported, the effects of abaloparatide on pre‐osteoblast MC3T3‐E1 are investigated in this study. It is found that in vitro abaloparatide treatment can promote pre‐osteoblast MC3T3‐E1 cells’ viability, differentiation, and mineralization significantly. For the drug delivery system, 3D porous structure of the methacrylated gelatin (GelMA) hydrogel is found effective for prolonging the release of abaloparatide (more than 10 days). Therefore, injectable photo‐crosslinked GelMA hydrogel is used in this study to prolong the release of abaloparatide and to promote healing of defected bones in rats. Overall, data collected in this study show no contradiction and imply that Abaloparatide‐loaded GelMA hydrogel is effective in stimulating bone regeneration.     

The JAK1/STAT3/SOCS3 axis in bone development,physiology, and pathology

Bone growth and the maintenance of bone structure are controlled by multiple endocrine and paracrine factors, including cytokines expressed locally within the bone microenvironment and those that are elevated, both locally and systemically, under inflammatory conditions. This review focuses on those bone-active cytokines that initiate JAK–STAT signaling, and outlines the discoveries made from studying skeletal defects caused by induced or spontaneous modifications in this pathway. Specifically, this review describes defects in JAK1, STAT3, and SOCS3 signaling in mouse models and in humans, including mutations designed to modify these pathways downstream of the gp130 coreceptor. It is shown that osteoclast formation is generally stimulated indirectly by these pathways through JAK1 and STAT3 actions in inflammatory and other accessory cells, including osteoblasts. In addition, in bone remodeling, osteoblast differentiation is increased secondary to stimulated osteoclast formation through an IL-6-dependent pathway. In growth plate chondrocytes, STAT3 signaling promotes the normal differentiation process that leads to bone lengthening. Within the osteoblast lineage, STAT3 signaling promotes bone formation in normal physiology and in response to mechanical loading through direct signaling in osteocytes. This activity, particularly that of the IL-6/gp130 family of cytokines, must be suppressed by SOCS3 for the normal formation of cortical bone.Subject terms: Growth factor signalling, Metabolic bone disease