Bone Mass Formation Research Articles

Evaluation of Potential Roles of Zinc Finger Homeobox 3 (Zfhx3) Expressed in Chondrocytes and Osteoblasts on Skeletal Growth in Mice.

Bone formation is tightly modulated by genetically encoded molecular proteins that interact to regulate cellular differentiation and secretion of bony matrix. Many transcription factors are known to coordinate these events by controlling gene transcription within networks. However, not all factors involved are known. Here, we identified a novel function forZinc Finger Homeobox 3(Zfhx3), a gene encoding a transcription factor, as a regulator of bone metabolism. We knocked outZfhx3conditionally in mice in either chondrocytes or osteoblasts and characterized their bones by micro-CT in 12-week-old mice. We observed a negative effect in linear bone growth in both knockout mice but reduced bone mass only in mice withZfhx3deleted in osteoblasts. Loss of Zfhx3 expression in osteoblasts affected trabecular bone mass in femurs and vertebrae in both sexes but influenced cortical bone volume fraction only in females. Moreover, transcriptional analysis of femoral bones in osteoblastZfhx3conditional knockout mice revealed a reduced expression of osteoblast genes, and histological evaluation of trabecular bones suggests that Zfhx3 causes changes in bone formation and not resorption. The loss of Zfhx3 causes reductions in trabecular bone area and osteoid volume, but no changes in the expression of osteoclast differentiation markers or number of TRAP stained osteoclasts. These studies introduce Zfhx3 as a relevant factor toward understanding gene regulatory networks that control bone formation and development of peak bone mass.

Sex-specific trisomic Dyrk1a-related skeletal phenotypes during development in a Down syndrome model.

Skeletal insufficiency affects all individuals with Down syndrome (DS) or trisomy 21 and may alter bone strength throughout development due to a reduced period of bone formation and early attainment of peak bone mass compared to those in typically developing individuals. Appendicular skeletal deficits also appear in males before females with DS. In femurs of male Ts65Dn DS model mice, cortical deficits were pronounced throughout development, but trabecular deficits and Dyrk1a overexpression were transitory until postnatal day (P) 30, when there were persistent trabecular and cortical deficits and Dyrk1a was trending toward overexpression. Correction of DS-related skeletal deficits by a purported DYRK1A inhibitor or through genetic means beginning at P21 was not effective at P30, but germline normalization of Dyrk1a improved male bone structure by P36. Trabecular and cortical deficits in female Ts65Dn mice were evident at P30 but subsided by P36, typifying periodic developmental skeletal normalizations that progressed to more prominent bone deficiencies. Sex-dependent differences in skeletal deficits with a delayed impact of trisomic Dyrk1a are important to find temporally specific treatment periods for bone and other phenotypes associated with trisomy 21.

Vitamin D Status among 2-18-Year-Old Romanian Pediatric Patients: A Single-Center Study.

An adequate vitamin D level is essential for optimal bone mass formation during growth. The present study aimed to assess (i) the sex-specific, age-specific, and potential seasonal (spring, summer, winter) influences on the pediatric circulating levels of 25-hydroxyvitamin D (25(OH)D); (ii) determine the frequency of pediatric patients with vitamin D deficiency (VDD) or insufficiency (VDI); and (iii) quantify the association between age category, sex, and season types and susceptibility to VDD and VDI, respectively. Laboratory data were collected on serum 25(OH)D levels in children aged between 2 and 18 years (n = 1674) who underwent blood sampling following admission to a university pediatric hospital in Cluj-Napoca (Romania) between January and June 2023. VDD (<20 ng/mL) was observed in 27% of pediatric patients. Among toddlers and preschoolers (2-5 years), VDD was 11%, while it was 33% among school-aged children (6-11 years) and 39% among adolescents (12-18 years). We found a significant difference in the frequencies of vitamin D status between females and males (p = 0.006). Also, we found significant associations of vitamin D status with age categories (p < 0.0001) and seasonal variations (p = 0.03). After adjusting for season of blood collection, the multinomial logistic regression model showed that children aged 6-11 years old (adjusted OR = 7, 95% CI: (4.9, 9.4)), children aged 12-18 years old (adjusted OR = 14, 95% CI: (9.3, 19.6)), and females (adjusted OR = 1.43, 95% CI: (1.10, 1.86)) were significantly associated with higher odds of VDD. In conclusion, the study revealed a significant difference in the frequency of VDD and VDI among pediatric patients older than six years, with a significant difference according to sex and season, being more pronounced among girls and during the winter and spring seasons.

Sex specific emergence of trisomic Dyrk1a-related skeletal phenotypes in the development of a Down syndrome mouse model.

Skeletal insufficiency affects all individuals with Down syndrome (DS) or Trisomy 21 (Ts21) and may alter bone strength throughout development due to a reduced period of bone formation and early attainment of peak bone mass compared to typically developing individuals. Appendicular skeletal deficits also appear in males before females with DS. In femurs of male Ts65Dn DS model mice, cortical deficits were pronounced throughout development, but trabecular deficits and Dyrk1a overexpression were transitory until postnatal day (P) 30 when there were persistent trabecular and cortical deficits and Dyrk1a was trending overexpression. Correction of DS-related skeletal deficits by a purported DYRK1A inhibitor or through genetic means beginning at P21 was not effective at P30, but germline normalization of Dyrk1a improved male bone structure by P36. Trabecular and cortical deficits in female Ts65Dn mice were evident at P30 but subsided by P36, typifying periodic developmental skeletal normalizations that progressed to more prominent bone deficiencies. Sex-dependent differences in skeletal deficits with a delayed impact of trisomic Dyrk1a are important to find temporally specific treatment periods for bone and other phenotypes associated with Ts21.

Enhancing Osteogenic Potential: Controlled Release of Dopamine D1 Receptor Agonist SKF38393 Compared to Free Administration.

Osteoporosis is the most common metabolic bone disorder and is characterized by decreased bone density, which has a relationship with the quality of life among the aging population. Previous research has found that activation of the dopamine D1 receptor can improve bone mass formation. SKF38393 is an agonist of dopamine D1 receptors. However, as a small-molecule drug, SKF38393 is unstable and releases quickly. The aim of this study was to prototype polylactic-co-glycolic acid (PLGA)/SKF38393 microspheres and assess their potential osteogenic effects compared to those under the free administration of SKF38393. The cytocompatibility of PLGA/SKF38393 was determined via CCK-8 and live/dead cell staining; the osteogenic effects in vitro were determined with ALP and alizarin red staining, qRT-PCR, and Western blotting; and the in vivo effects were assessed using 25 Balb/c mice. We also used a PCR array to explore the possible signaling pathway changes after employing PLGA/SKF38393. Our experiments demonstrated that the osteogenic effect of D1Rs activated by the PLGA/SKF38393 microsphere was better than that under free administration, both in vitro and in vivo. According to the PCR array, this result might be associated with six signaling pathways (graphical abstract). Ultimately, in this study, we prototyped PLGA/SKF38393, demonstrated its effectiveness, and preliminarily analyzed its mechanism of action.

Catgut embedding in acupoints combined with repetitive transcranial magnetic stimulation for the treatment of postmenopausal osteoporosis: study protocol for a randomized clinical trial.

To date, the clinical modulation for bone metabolism based on the neuro-bone mass regulation theory is still not popular. The stimulation of nerve systems to explore novel treatments for Postmenopausal osteoporosis (PMOP) is urgent and significant. Preliminary research results suggested that changes brain function and structure may play a crucial role in bone metabolism with PMOP. Thus, we set up a clinical trial to investigate the effect of the combination of repetitive transcranial magnetic stimulation (rTMS) and catgut embedding in acupoints (CEA) for PMOP and to elucidate the central mechanism of this neural stimulation in regulating bone metabolism. This trial is a prospective and randomized controlled trial. 96 PMOP participants will be randomized in a 1:1:1 ratio into a CEA group, an rTMS group, or a combined one. Participants will receive CEA, rTMS, or combined therapy for 3 months with 8 weeks of follow-up. The primary outcomes will be the changes in Bone Mineral Density scores, total efficiency of Chinese Medicine Symptoms before and after treatment. Secondary outcomes include the McGill Pain Questionnaire Short-Form, Osteoporosis Symptom Score, Mini-Mental State Examination, and Beck Depression Inventory-II. The leptin, leptin receptor, and norepinephrine levels of peripheral blood must be measured before and after treatment. Adverse events that occur during the trial will be recorded. CEA achieves brain-bone mass regulation through the bottom-up way of peripheral-central while rTMS achieves it through the top-down stimulation of central-peripheral. CEA combined with rTMS can stimulate the peripheral-central at the same time and promote peripheral bone mass formation. The combination of CEA and rTMS may play a coordinating, synergistic, and side-effect-reducing role, which is of great clinical significance in exploring better treatment options for PMOP.Clinical trial registration: https://www.chictr.org.cn/, identifier ChiCTR2300073863.

CHRONIC HIGH-FAT DIET CONSUMPTION ACCELERATES OSTEOBLAST DYSFUNCTION AND OSTEOPOROSIS BY GUT MICROBIAL METABOLITE TRIMETHYLAMINE-N-OXIDE

Obesity is correlated with the development of osteoporotic diseases. Gut microbiota-derived metabolite trimethylamine-n-oxide (TMAO) accelerates obesity-mediated tissue deterioration. This study was aimed to investigate what role TMAO may play in osteoporosis development during obesity.Mice were fed with high-fat diet (HFD; 60 kcal% fat) or chow diet (CD; 10 kcal% fat) or 0.2% TMAO in drinking water for 6 months. Body adiposis and bone microstructure were investigated using μCT imaging. Gut microbiome and serum metabolome were characterized using 16S rRNA sequencing and liquid chromatography-tandem mass spectrometry. Osteogenic differentiation of bone-marrow mesenchymal cells was quantified using RT-PCR and von Kossa staining. Cellular senescence was evaluated by key senescence markers p16, p21, p53, and senescence association β-galactosidase staining.HFD-fed mice developed hyperglycemia, body adiposis and osteoporosis signs, including low bone mineral density, sparse trabecular microarchitecture, and decreased biomechanical strength. HFD consumption induced gut microbiota dysbiosis, which revealed a high Firmicutes/Bacteroidetes ratio and decreased α-diversity and abundances of beneficial microorganisms Akkermansiaceae, Lactobacillaceae, and Bifidobacteriaceae. Serum metabolome uncovered increased serum L-carnitine and TMAO levels in HFD-fed mice. Of note, transplantation of fecal microbiota from CD-fed mice compromised HFD consumption-induced TMAO overproduction and attenuated loss in bone mass, trabecular microstructure, and bone formation rate. TMAO treatment inhibited trabecular and cortical bone mass and biomechanical characteristics; and repressed osteogenic differentiation capacity of bone-marrow mesenchymal cells. Mechanistically, TMAO accelerated mitochondrial dysfunction and senescence program, interrupted mineralized matrix production in osteoblasts.Gut microbial metabolite TMAO induced osteoblast dysfunction, accelerating the development of obesity-induced skeletal deterioration. This study, for the first time, conveys a productive insight into the catabolic role of gut microflora metabolite TMAO in regulating osteoblast activity and bone tissue integrity during obesity.

Peak Bone Mass Formation: Modern View of the Problem.

Peak bone mass is the amount of bone tissue that is formed when a stable skeletal state is achieved at a young age. To date, there are no established peak bone mass standards nor clear data on the age at which peak bone mass occurs. At the same time, the level of peak bone mass at a young age is an important predictor of the onset of primary osteoporosis. The purpose of this review is to analyze the results of studies of levels of peak bone mass in general, the age of its onset, as well as factors influencing its formation. Factors such as hormonal levels, body composition, physical activity, nutrition, heredity, smoking, lifestyle, prenatal predictors, intestinal microbiota, and vitamin and micronutrient status were considered, and a comprehensive scheme of the influence of these factors on the level of peak bone mass was created. Determining the standards and timing of the formation of peak bone mass, and the factors affecting it, will help in the development of measures to prevent its shortage and the consequent prevention of osteoporosis and concomitant diseases.

Formation and Acquisition of Bone Mass: A Commitment of the Obstetrician-Gynecologist in an Interdisciplinary Program

This article provides an overview of the process of bone mass development and acquisition, starting from gestation until reaching peak bone mass, as well as the presence of certain disorders. Bone mass formation has been studied at various stages of development, from pregnancy, childhood, adolescence, and adulthood, where the greatest increase occurs to achieve peak bone mass. The increase in bone mass begins during the gestation process as a period of high fetal calcium demand and continues from birth through childhood and infancy, experiencing its maximum growth during adolescence until reaching the peak of bone mass in adulthood, around 20-30 years of age. Approximately 70% of bone mass is inherited from parents, while the remaining percentage is acquired through the processes of gestation, development, and growth, where environmental factors, nutrition, exercise, avoidance of toxic substances, and maintaining overall health contribute to achieving the highest concentration of bone mass. This becomes a reserve to respond to bone loss that typically starts around the age of 40, with the greatest loss during the transition to menopause and later, at a slower rate, during old age.

Polymorphisms in Genes Encoding VDR, CALCR and Antioxidant Enzymes as Predictors of Bone Tissue Condition in Young, Healthy Men.

The aim of the study was to assess significant predictors of bone mineral content (BMC) and bone mineral density (BMD) in a group of young, healthy men at the time of reaching peak bone mass. Regression analyses showed that age, BMI and practicing combat sports and team sports at a competitive level (trained vs. untrained group; TR vs. CON, respectively) were positive predictors of BMD/BMC values at various skeletal sites. In addition, genetic polymorphisms were among the predictors. In the whole population studied, at almost all measured skeletal sites, the SOD2 AG genotype proved to be a negative predictor of BMC, while the VDR FokI GG genotype was a negative predictor of BMD. In contrast, the CALCR AG genotype was a positive predictor of arm BMD. ANOVA analyses showed that, regarding SOD2 polymorphism, the TR group was responsible for the significant intergenotypic differences in BMC that were observed in the whole study population (i.e., lower BMC values of leg, trunk and whole body were observed in AG TR compared to AA TR). On the other hand, higher BMC at L1-L4 was observed in the SOD2 GG genotype of the TR group compared to in the same genotype of the CON group. For the FokI polymorphism, BMD at L1-L4 was higher in AG TR than in AG CON. In turn, the CALCR AA genotype in the TR group had higher arm BMD compared to the same genotype in the CON group. In conclusion, SOD2, VDR FokI and CALCR polymorphisms seem to affect the association of BMC/BMD values with training status. In general, at least within the VDR FokI and CALCR polymorphisms, less favorable genotypes in terms of BMD (i.e., FokI AG and CALCR AA) appear to be associated with a greater BMD response to sports training. This suggests that, in healthy men during the period of bone mass formation, sports training (combat and team sports) may attenuate the negative impact of genetic factors on bone tissue condition, possibly reducing the risk of osteoporosis in later age.

Lack of Skeletal Effects in Mice with Targeted Disruptionof Prolyl Hydroxylase Domain 1 (Phd1) Gene Expressed in Chondrocytes.

The critical importance of hypoxia-inducible factor (HIF)s in the regulation of endochondral bone formation is now well established. HIF protein levels are closely regulated by the prolyl hydroxylase domain-containing protein (PHD) mediated ubiquitin-proteasomal degradation pathway. Of the three PHD family members expressed in bone, we previously showed that mice with conditional disruption of the Phd2 gene in chondrocytes led to a massive increase in the trabecular bone mass of the long bones. By contrast, loss of Phd3 expression in chondrocytes had no skeletal effects. To investigate the role of Phd1 expressed in chondrocytes on skeletal development, we conditionally disrupted the Phd1 gene in chondrocytes by crossing Phd1 floxed mice with Collagen 2α1-Cre mice for evaluation of a skeletal phenotype. At 12 weeks of age, neither body weight nor body length was significantly different in the Cre+; Phd1flox/flox conditional knockout (cKO) mice compared to Cre−; Phd1flox/flox wild-type (WT) control mice. Micro-CT measurements revealed significant gender differences in the trabecular bone volume adjusted for tissue volume at the secondary spongiosa of the femur and the tibia for both genotypes, but no genotype differences were found for any of the trabecular bone measurements of either femur or tibia. Similarly, cortical bone parameters were not affected in the Phd1 cKO mice compared to control mice. Histomorphometric analyses revealed no significant differences in bone area, bone formation rate or mineral apposition rate in the secondary spongiosa of femurs between cKO and WT control mice. Loss of Phd1 expression in chondrocytes did not affect the expression of markers of chondrocytes (collage 2, collagen 10) or osteoblasts (alkaline phosphatase, bone sialoprotein) in the bones of cKO mice. Based on these and our published data, we conclude that of the three PHD family members, only Phd2 expressed in chondrocytes regulates endochondral bone formation and development of peak bone mass in mice.

Radiological evaluation of atlantoaxial fusion using C2 translaminar screws and C2 pedicle screws: Does the screw halo sign imply fusion failure?

The purpose of this study was to identify the criteria for atlantoaxial (AA) fusion by comparing follow-up lateral radiographs and computed tomography (CT) images. We retrospectively analyzed data from 161 consecutive patients undergoing AA fusion. Patients with a minimum of 1 year of CT follow-up after AA fusion surgery using C2 pedicle screws or translaminar screws (C2TLS) were included. Patients were followed up radiographically at 3, 6, and 12 months after surgery, and dynamic lateral radiographs were also evaluated. A total of 49 patients were analyzed, with a mean CT image follow-up of 41.6 ± 37.6 months. Thirty eight patients had C2 pedicle screw placement, and 11 patients underwent planned C2TLS. AA fusion with bridging bone mass formation was achieved in 45/49 (91.8%) patients. Screw halos were observed in 14/49 (28.6%) patients. Among them, final fusion failure occurred in 2 (14.3%) patients. The last follow-up CT showed no difference in the fusion failure rate according to the presence or absence of a screw halo (no halo, 5.7%; halo, 14.3%; P = .33). The differences in C1-2 segmental angles (SA) in flexion-extension dynamic lateral radiographs were 1.99 ± 1.62° in the fusion group and 4.37 ± 2.13° in the non-fusion group (P = .01). The likelihood of fusion failure increased when the SA gap was greater than 2.62° (P = .05). C2TLS placement had a significantly higher incidence of screw halos. However, the halo sign was not significantly related to final bone fusion. Bone fusion could be predicted when the SA gap of C1-2 was less than 2.62° on the dynamic radiograph.

Bone Marrow Mesenchymal Stem Cell-Exosomes (BMSC-ExO) Promote Osteogenic Differentiation In Vitro and Osteogenesis In Vivo by Regulating miR-318/Runt-Related Transcription Factor 2 (RUNX2)

Primary osteoporosis (PMOP) is characterized by bone mass reduction and bone microstructure destruction, increased bone fragility and prone to fracture, which is partially caused by ovarian dysfunction and decreased estrogen content. Bone marrow mesenchymal stem cell exosomes (BMSC-ExO) can improve PMOP. In this study, BMSC-EXO was used to study the role and function of miR-318 and Runx2 in PMOP. Human osteogenitor cells were isolated from PMOP patients with primary osteoporosis. After BMSC-exo treatment, miR-318 and Runx 2 level was tested by RT-qPCR and Western blot. In addition, mice in OVX group were treated with BMSC-ExO (bilateral ovaries were removed) to observe the effect of BMSC-ExO on bone tissue. Our results showed that BMSC-exo treatment significantly decreased miR-318 level, upregulated RUNX2 expression and increased ALP activity. In addition, BMSC-exo administration ameliorated the declined bone mass and bone formation in osteoporotic femurs in OVX mice. In conclusion, BMSC-Exo enhances Runx2 levels by down-regulation of miR-318, thereby promoting osteogenic differentiation of osteogenitor cells, providing new potential therapeutic targets for treating PMOP.

STIFF ELBOW!! POST TRAUMATIC MYOSITIS OSSIFICANS? A CASE REPORT

Myositis Ossicans is dened as Ossication of Haematoma around a joint resulting in formation of bone mass leading to restriction of joint movements completely in majority of cases. This is also known as Heterotopic Ossication, Ectopic Ossication. It is pathological bone formation in soft tissues especially in between muscle planes. It is extensive, progressive benign lesion occurring most commonly in exor muscles of arm, quadriceps muscles, adductor muscles of hip joint in young active adults and athletes [2,3,10] . Massage following trauma is the most aggravating factor of Myositis Ossicans. We report a case of 12 year boy with complaining of stiff elbow since 9 months, restricted elbow joint movements with history of fall while playing 1 year back for which he had taken treatment from local quack with aggressive massaging. There is xed exion deformity of 90°. Clinical examination revealed a palpable bony mass on anterior aspect of elbow and Radiological investigation revealed ossied bony mass bridging elbow joint. Surgical Excision is done and biopsy showed mature stage Myositis Ossicans trabecular bone. Elbow range of movements started and patients has good range of movements with 1 year follow up with good physiotherapy.

The Correlation of Caffeine and Fizzy Drink Consumption and Bone Mineral Density in Women Fertilizer Age in Pekanbaru City

Osteoporosis is defined as a decrease in bone mass and is characterized by an increased risk of fracture due to bone fragility. Prevention of low bone density can be done by optimizing the formation of bone mass at the time of growth, namely the age of 20-35 years. Research on osteoporosis in Jakarta in 2011 on subjects aged 20-25 years, stated that 6.3% had osteoporosis and 51.1% had osteopenia (pre-osteoporosis). The aim of the study was to identify the correlation of caffeine and soft drinks consumption toward bone mineral density status in women of childbearing age. This study was a quantitative analytic study, with a cross sectional research design. The sample was women of childbearing age who were in the work area of Tampan District as many as 399 people. The Chi-Square test showed the effect of caffeine consumption and soft drinks on the status of bone mineral density in women of childbearing age with a P value of 0.000 &lt; Alpha 0.05 with a large OR of 24,330 (95% CI: 10,174- 58.182), meaning that respondents who consumed caffeine and soft drinks were 24 times more likely to suffer from osteoporosis. It is expected for women to avoid risk factors that can cause a decrease in bone mineral density and perform early detection of osteoporosis before the age of 30 years.

Quantitative ultrasound assessment of bone tissue in premature newborn twins

Multiple pregnancy is associated with a high risk premature newborn twins (PNT) birth and the formation of low bone mass. Determining the state of bone tissue (BT) after birth is important for understanding the dynamics of its changes in the PNTs’ growth. Aim: to conduct and analyze the results of quantitative ultrasound assessment of BT in PNT. Materials and methods. In the early neonatal age, 24 pairs of twins and 39 children from singleton pregnancies (SP) born at gestational age (GA) of 30–36 weeks were examined. Pair of twins with a difference in body weight of 5% or more were involved. BT status was determined with an ultrasonic densitometer “Sunlight Omnisense 9000”, measuring SOS, m/s. Results. In GA up to 34 weeks SOS of BT in both twins did not differ from each other or from newborns from SP of the corresponding GA. In PNT, from 34 weeks of gestation and more, SOS increased (P &lt; 0.05) in siblings with lower body weight compared to bigger one – 2925 (2887; 3036) m/s and 2866 (2801; 2895) m/s, respectively. According to correlations, the body weight of PNT was not determined as a significant factor influencing the state of BT. SOS in PNT had a weak positive correlation (R = 0.29, P &lt; 0.05) with their GA in contrast to the strong direct correlation (R = 0.78, P &lt; 0.05) in newborns from SP. Among the factors influencing the state of BT according to SOS in PNT, the inverse correlations with the factor of increasing the number of pregnancies (R = -0.59, P &lt; 0.05) and with birth from monochorionic multiple pregnancies (R = -0.57, P &lt; 0.05) were determined. Conclusions. SOS in children born in GA of 34 weeks and older was 2925 (2887; 3036) m/s in PNT with lower body weight in pairs. This value was higher (P &lt; 0.05) than in bigger siblings and PNT born in GA less than 34 weeks. SOS in PNT had a weak correlation (P &lt; 0.05) with their GA in contrast to children born in the same GA from SP and had no correlation with the body weight of twins. The average correlation (P &lt; 0.05) between low SOS in PNT and the number of previous pregnancies, as well as with birth from monochorionic multiple pregnancies.

CircRNA hsa_circ_0001421 promotes the osteoblast differentiation of human adipose mesenchymal stem cells through the miR-608/SP7 axis

Human adipose mesenchymal stem cells (hAMSCs) can differentiate into osteoblasts, which can enhance bone mass and bone formation. Circular RNA plays an important role in the osteoblast differentiation of mesenchymal stem cells, but the mechanism remains unclear. We used hAMSCs to study the role of circRNA hsa_circ_0001421/miR-608/SP7 axis in osteoblast differentiation. qRT-PCR, western blotting, alkaline phosphatase (ALP) activity measurement, and alizarin red staining (ARS) were used to evaluate the osteoblast differentiation ability of hAMSCs. Dual luciferase reporter gene assay to analyze the relationship of miR-608 with circRNA hsa_circ_0001421 and SP7. Our results showed that circRNA hsa_circ_0001421 could promote the osteoblast differentiation of hAMSCs. qRT-PCR and western blotting showed that the expression of osteogenic genes (ALP, RUNX2, and OCN) was upregulated, and ALP activity and ARS were significantly increased. The dual luciferase reporter gene assay showed that miR-608 competitively binds with circRNA hsa_circ_0001421 and SP7. MiR-608 inhibited the expression of SP7 and repressed the osteoblast differentiation of hAMSCs, whereas circRNA hsa_circ_0001421 inhibited the expression of miR-608 and reversed the downregulation of SP7 by miR-608. Taken together, the circRNA hsa_circ_0001421/miR-608/SP7 axis at least partially regulates the osteoblast differentiation of hAMSCs, which may be a potential target of hAMSCs for the treatment of osteoporosis.

Cryptotanshinone Suppressed Postmenopausal Osteoporosis by Preventing RANKL-Mediated Osteoclastogenesis against Kidney Injury.

Background Cryptotanshinone (CPT), an active component extracted from the root of Salvia miltiorrhiza Bunge, exhibits extensive favorable bioactive properties including anti-inflammatory, antioxidative, antibacterial, and antitumor effects. This study aims to investigate the effects of CPT on osteogenesis and explore related mechanisms both in vivo and in vitro. Methods In the in vivo experiment, ovariectomized (OVX) female rats were intragastrically administered with CPT at doses of 10 mg/kg and 20 mg/kg for 13 consecutive weeks. Dual-energy X-ray absorptiometry was employed to detect bone mineral density (BMD). ELISA assay was leveraged to detect the biochemical parameters such as BUN and creatinine in the kidney samples. Bone and kidney sections were dyed by H&E and Masson staining kits. In the in vitro experiment, the RAW 264.7 cells were stimulated through the receptor activation of the nuclear factor kappa B ligand (RANKL) to establish an osteoclast differentiation model, and CPT's protective effect against bone loss was evaluated. Differentiated osteoclasts were determined by TRAP staining. While, osteoclast-marker proteins such as NFATc1, c-Fos, and cathepsin K were identified by Western blot. Results The results from in vivo experiments revealed that CPT could elevate bone mass and increase bone formation markers in OVX rats. Intriguingly, CPT administration noticeably ameliorated the kidney injury in OVX rats by suppressing BUN and restoring creatinine levels. Furthermore, the results from in vitro experiments suggested that CPT downregulated the protein expression of osteoclast-associated genes such as cathepsin K, c-Fos, and NFATc1 which hinted the related potential mechanisms. Conclusion The evidence from in vivo and in vitro experiments suggested that CPT exerted antiosteoclastogenic effects by inhibiting the activation of osteoclast differentiation followed by suppressing the protein expressions of cathepsin K, c-Fos, and NFATc1 in osteoclast precursors, and it exhibited protective effects against kidney damage, which highlighted its advantage in clinical application.

ZEB1 Mediates Bone Marrow Mesenchymal Stem Cell Osteogenic Differentiation Partly via Wnt/β-Catenin Signaling.

Zinc finger E-box-binding homebox 1 (ZEB1) is a zinc-finger transcription factor best known for its role in promoting the epithelial-mesenchymal transition, which is also related to osteogenesis. Here, ZEB1 was investigated for its role in the commitment of bone marrow mesenchymal stem cells (BMSCs) to osteoblasts. In vitro, ZEB1 expression decreased following osteogenic differentiation. Furthermore, silencing of ZEB1 in BMSCs promoted osteogenic activity and mineralization. The increase in osteogenic differentiation induced by si-ZEB1 could be partly rescued by the inhibition of Wnt/β-catenin (si-β-catenin). In vivo, knockdown of ZEB1 in BMSCs inhibited the rapid bone loss of ovariectomized (OVX) mice. ZEB1 expression has also been negatively associated with bone mass and bone formation in postmenopausal women. In conclusion, ZEB1 is an essential transcription factor in BMSC differentiation and may serve as a potential anabolic strategy for treating and preventing postmenopausal osteoporosis (PMOP).

Using percutaneous parapedicle screw vertebroplasty to treat transpedicle screw loosening.

Pedicle screw loosening (PSL) is a postsurgical complication of spinal fusion surgery that can result in morbidity. The aim of this study was to evaluate the efficacy and safety of percutaneous parapedicle screw vertebroplasty (PPSV) for pain reduction and motility improvement in patients with PSL. The postsurgical solid inter-body fusion with inter-body bone mass formation of 32 patients who underwent lumbar-sacrum spinal fusion surgery was confirmed with plain films and CT scans. Each patient had one or two screws with symptomatic PSL and was treated with PPSV. All the patients were then followed up for 12 to 24 months. The visual analog scale (VAS) and Roland-Morris Disability Questionnaire (RMDQ) were used to evaluate each patient before the operation, after the operation, and during the follow-up period. A total of 32 patients with a total of 47 screws with PSL were treated with PPSV and experienced different results in terms of pain reduction (with the mean VAS score dropping from 7.97 ± 0.74 to 2.34 ± 1.59, p < 0.001) and motility improvement (with the mean RMDQ score dropping from 16.75 ± 1.84 to 7.21 ± 4.08, p < 0.001). The motility improvement was significantly correlated with pain reduction (r = 0.42, p = 0.018), with the mean follow-up period being 19.3 ± 6.2 months (range: 8-36 months). However, five patients who experienced moderate improvements had eventually received a revision operation after undergoing PPSV. The PPSV procedure is effective and safe for the reduction of pain and improvement of life quality in patients with PSL. It can thus be considered as a possible option for the revision of spinal fusion surgery.