Tuberous sclerosis complex 1 targeted depletion in macrophages promotes osteogenesis by modulating secretion of Oncostatin M in the inflammatory stage of bone healing.

In bone healing, earlier bone formation benefits bone repair. The first process of repair following bone injury involves the interaction between macrophage polarization and osteogenic activation of osteoblast linage cells, but the radical difference between the contributions of classically-activated M1 macrophages and alternatively-activated M2 macrophages to osteogenesis remains obscure. To test our hypothesis that M1 macrophages promote bone healing, we generated transgenic mice with myeloid lineage-specific TSC1 deletion (TSC1KO) to investigate the functional roles of M1 macrophages in the process of bone defect healing. We demonstrated that constitutive activation of mammalian target of rapamycin complex 1 (mTORC1) enhances M1 macrophage polarization during bone healing. By creating tibial bone defect as a model of bone repair in TSC1KO mice and their littermates, we surprisingly found osteogenic responses in the defective bone region of TSC1KO mice, where repair occurred by intramembranous ossification (IO) in the mice was promoted due to the enhanced M1-polarized macrophage polarization. We propose that Oncostatin M (OSM) secreted by M1-polarized macrophages but not M2 macrophages likely functions as a paracrine factor in this promoted repair process, as verified by the induction of osteoblastic differentiation and matrix mineralization. Interestingly, the expression level of the OSM receptor (OSMR) was continually upregulated in osteoblast linage cells with M1 medium. Additionally, OSMR activated the signaling transduction system of JAK/STAT/RUNX2 in MSCs, which in turn stimulates the recruitment of osteoblast lineage cells and activates IO. These results indicate that TSC1 targeted depletion in macrophages promotes bone healing by inducing secretion of OSM. This study highlights that regulation of M1 macrophage polarization is a novel basis for the improvement of bone regeneration and that regulation of macrophage polarization can be a potential therapeutic strategy to treat defects in the repair phase of bone healing.

Analysis of risk factors for non-fusion of bone graft in anterior cervical discectomy and fusion: A clinical retrospective study.

BACKGROUND: Bone graft fusion is a major concern among surgeons after Anterior Cervical Discectomy and Fusion (ACDF) surgery as non-fusion may lead to further physical and drug therapies. METHODS: The related risk elements of non-fusion of bone graft in ACDF surgery were retrospectively assessed. Patients receiving ACDF operation in our hospital from January 2015 to December 2019 were retrospectively analyzed. According to the criteria, 107 study subjects were recruited with a total of 164 surgical segments. The general information of patients, bone graft materials, imaging parameters, and clinical efficacy was recorded. T-test, chi-square test and binary logistic regression evaluation were employed to explore the risk factors of bone graft nonunion. RESULTS: Low housefield unit (HU) value, diabetes, allogeneic bone, and hydroxyapatite (HA) artificial bone could be risk factors for bone graft fusion in ACDF surgery. Further multivariate analysis was performed and confirmed those related factors of bone graft non-fusion including low HU value (non-fusion rate: 32.53% [27/83], OR = 5.024, p = 0.025), diabetes (non-fusion rate: 53.33% [8/15], OR = 4.776, p = 0.031), allogeneic bone (18.57% [13/70], OR = 3.964, p = 0.046), and artificial bone (68.29% [28/41], OR = 50.550, p < 0.01). CONCLUSION: By looking at bone graft fusion, selecting autologous iliac bone is an ideal selection to avoid non-fusion of bone graft in ACDF. Diabetes was more important predictor of bone graft nonunion than low HU value. Larger sample size and longer follow-up are required to further confirm these findings in the future.

Association of circulating tumor cells and IMP3 expression with metastasis of osteosarcoma.

Background: Circulating tumor cells (CTCs) have been identified as a prognostic biomarker of tumors such as breast cancer and nasopharyngeal carcinoma, because they are obtained through a simple and noninvasive blood draw or liquid biopsy, but its clinical significance in osteosarcoma is still unclear. In this study, we analyzed the relationship between CTCs and clinicopathological features and discussed whether CTCs could be used as a biomarker for metastasis in osteosarcoma. Methods: We enrolled 50 osteosarcoma patients with Enneking Stage IIB and Stage III and detected CTCs in 5 ml of peripheral blood samples collected from patients using the Canpatrol® CTC detection platform. Subsequently, multiplex RNA in situ hybridization (RNA-ISH) based on various molecular markers was performed to identify and classify CTCs. The relationships between clinical pathological features and CTC counts, subtypes (epithelial type, E type; hybrid epithelial/mesenchymal type, H type; mesenchymal type, M type), and insulin-like growth factor mRNA-binding protein 3 (IMP3) expression in CTCs were analyzed. Results: CTCs were detected in 86% (43/50) of the osteosarcoma patients. The CTC counts, especially the total CTCs and H-type CTCs, signifcantly differed between Enneking Stage IIB and Stage III patients (P < 0.05). No significant differences were observed between the CTC count or type and other clinicopathological features (P > 0.05). There were significant differences in the expression of IMP3 in different types of CTCs, and the IMP3 positive rates in E/H/M type CTCs were 38.4, 65.6, and 62.0%, respectively (P < 0.001). Receiver operating characteristic (ROC) curve analysis showed that IMP3-positive CTC count had the best performance for diagnostic metastasis, with the largest area under the curve of 0.873 and cutoff value of four cells/5ml blood (sensitivity = 87.5%; specificity = 82.4%). Serial CTC monitoring in one patient suggested that total CTCs and H-type CTCs were associated with disease progression. Conclusion: This study demonstrates that the CTCs, especially the IMP3-positive CTCs and H/M-type CTCs, are related to the metastasis of osteosarcoma.

En bloc resection of huge primary tumors with epidural involvement in the mobile spine using the "rotation-reversion" technique: Feasibility, safety, and clinical outcome of 11 cases.

Background: En bloc resection of spinal tumors provides better local control and survival outcomes than intralesional resection. Safe margins during en bloc resection of primary spinal tumors with epidural involvement are required for improved outcomes. The present study describes a "rotation-reversion" technique that has been used for en bloc resection of huge primary tumors in the mobile spine with epidural involvement and reported the clinical outcomes in these patients. Methods: All patients with primary spinal tumors who were treated with the rotation-reversion technique at our institution between 2015 and 2021 were evaluated retrospectively. Of the patients identified, those with both huge extraosseous soft-tissue masses and epidural involvement were selected for a case review. Clinical and radiological characteristics, pathologic findings, operative procedures, complications, and oncological and functional outcomes of these patients were reviewed. Results: Of the 86 patients identified with primary spinal tumors who underwent en bloc resection using the rotation-reversion technique between 2015 and 2021, 11 had huge extraosseous soft-tissue masses with epidural involvement in the mobile spine. The average maximum size of these 11 tumors was 8.1 × 7.5 × 9.7 cm. Median follow-up time was 28.1 months, mean operation time was 849.1 min (range 465-1,340 min), and mean blood loss was 6,972.7 ml (range 2,500-17,700 ml), with 10 (91%) of the 11 patients experiencing perioperative complications. The negative margin rate was 91%, with only one patient (9%) experiencing local recurrence. Ten patients were able to walk normally or with a crutch at the last follow-up, whereas one was completely paralyzed preoperatively. Conclusion: The rotation-reversion technique is an effective procedure for the en bloc resection of huge primary spinal tumors, with the extension of invasion in selected patients including not only the vertebral body but also the pedicle and part of the posterior arch.

Identification of safe channels for screws in the anterior pelvic ring fixation system.

BACKGROUND: Minimally invasive surgery for pelvic fracture using anterior ring internal fixator system is increasing gradually, and the way to insert the fixation screws in the fixation system is the key technical points of the method. However, there have been few studies on insertion of fixation screws for the anterior pelvic ring internal fixator system. OBJECTIVE: To identify safe channels for fixation screws in the anterior pelvic fixator system and provide the anatomical basis for insertion of fixation screws in clinical operation. METHODS: Screw insertion was simulated into a total of 40 pelvic finite element models as well as 16 fresh pelvic specimens, and the channel parameters were measured. RESULTS: Finite elements (male, female) include: screws in ilium: length 114.4 ± 4.1 and 107.6 ± 8.3 mm, respectively; diameter 11.7 ± 0.5 and 10.0 ± 0.6 mm, distance between screw and anterior inferior iliac spine: 5.5 ± 1.0 and 5.6 ± 1.0 mm, angle of coronal plane 55.8° ± 2.4° and 50.6° ± 3.1°, angle of sagittal plane 26.6° ± 1.0° and 24.5° ± 1.9° and angle of horizontal plane 64.9 ± 3.7 and 58.1 ± 3.1; screws in pubis: length 47.0 ± 2.0 and 39.8 ± 3.9 mm, diameter 7.1 ± 0.4 and 6.1 ± 0.4 mm. Specimens (male, female) include: distance between screw and anterior inferior iliac spine: 5.5 ± 0.5 and 5.6 ± 0.7 mm, angle of coronal plane 55.9° ± 1.3° and 50.7° ± 1.5°, angle of sagittal plane 26.7° ± 0.5° and 24.1° ± 0.9° and angle of horizontal plane 64.8° ± 0.6° and 58.8° ± 0.8°. In the comparison between female and male in each group, differences in distances between screws and anterior inferior iliac spine and median line of symphysis pubis (P > 0.05) were not statistically significant; differences in the remaining parameters were statistically significant (P < 0.05). CONCLUSIONS: If surgeons paid attention to sex differences, select screws of appropriate diameter and length and hold the insertion position and direction, screws in the anterior pelvic ring fixation system could be safely inserted.

mTORC1 induces plasma membrane depolarization and promotes preosteoblast senescence by regulating the sodium channel Scn1a.

Senescence impairs preosteoblast expansion and differentiation into functional osteoblasts, blunts their responses to bone formation-stimulating factors and stimulates their secretion of osteoclast-activating factors. Due to these adverse effects, preosteoblast senescence is a crucial target for the treatment of age-related bone loss; however, the underlying mechanism remains unclear. We found that mTORC1 accelerated preosteoblast senescence in vitro and in a mouse model. Mechanistically, mTORC1 induced a change in the membrane potential from polarization to depolarization, thus promoting cell senescence by increasing Ca2+ influx and activating downstream NFAT/ATF3/p53 signaling. We further identified the sodium channel Scn1a as a mediator of membrane depolarization in senescent preosteoblasts. Scn1a expression was found to be positively regulated by mTORC1 upstream of C/EBPα, whereas its permeability to Na+ was found to be gated by protein kinase A (PKA)-induced phosphorylation. Prosenescent stresses increased the permeability of Scn1a to Na+ by suppressing PKA activity and induced depolarization in preosteoblasts. Together, our findings identify a novel pathway involving mTORC1, Scn1a expression and gating, plasma membrane depolarization, increased Ca2+ influx and NFAT/ATF3/p53 signaling in the regulation of preosteoblast senescence. Pharmaceutical studies of the related pathways and agents might lead to novel potential treatments for age-related bone loss.

3D surface reconstruction of the femur and tibia from parallel 2D contours.

BACKGROUND: Segmented structures, such as bones, are typically stored as 2D contours contained on evenly spaced images (slices). Contour interpolation algorithms to turn 2D contours into a 3D surface may differ in their results, causing discrepancies in analysis. This study aimed to create an accurate and consistent algorithm for the interpolation of femur and tibial contours that can be used in computer-assisted surgical navigation systems. METHODS: The implemented algorithm performs contour interpolation in a step-by-step manner, determining an optimal surface between each pair of consecutive contours. Determining such a surface is reduced to the problem of finding certain minimum-cost cycles in a directed toroidal graph. The algorithm assumes that the contours are ordered. The first step in the algorithm is the determination of branching patterns, followed by the removal of keyholes from contours, optimization of a target function based on the surface area, and mesh triangulation based on the optimization results and mesh seal. RESULTS: The algorithm was tested on contours segmented on computed tomography images from femoral and tibial specimens; it was able to generate qualitatively good 3D meshes from the set of 2D contours for all the tested examples. CONCLUSION: The contour interpolation algorithm proved to be quite effective using optimization based on minimizing the area of the triangles that form the 3D surface. The algorithm can be used for the 3D reconstruction of other types of 2D cuts, but special attention must be paid with the branches, since the proposed algorithm is not designed for complex branching structures.

Clinical application of anterior ring internal fixator system combined with sacroiliac screw fixation in Tile C pelvic fracture treatment.

BACKGROUND: How to perform minimally invasive surgery for Tile C pelvic fracture is a major problem in clinical practice. We performed minimally invasive surgery for Tile C pelvic fracture using anterior ring internal fixator systems combined with sacroiliac screw fixation. OBJECTIVE: To investigate the advantages and efficacy of anterior ring internal fixator systems combined with sacroiliac screw fixation in the treatment of Tile C pelvic fracture. METHODS: From May 2017 to May 2020, 27 patients with Tile C pelvic fracture who underwent anterior ring internal fixator system combined with sacroiliac screw fixation (group A) and 21 patients with Tile C pelvic fracture who underwent plate-screw system combined with sacroiliac screw fixation (group B) were retrospectively analyzed. RESULTS: All 48 patients were followed up for more than 12 months, all fractures healed within 3-6 months. The operative time, intraoperative bleeding volume, blood transfusion volume, incision length, hospital stay, complication rate and Majeed score were 63.5 ± 10.7 min, 48.3 ± 27.9 ml, 0 ml, 4.5 ± 0.8 cm, 10.2 ± 2.7 d, 3.7% and 89.7 ± 4.6 points, respectively, in group A and 114.8 ± 19.1 min, 375 ± 315.8 ml, 266.7 ± 326.6 ml, 9.2 ± 3.9 cm, 20.9 ± 5.7 d, 23.8% and 88.7 ± 4.9 points, respectively, in group B. Combined excellent and good rates of the Matta evaluation and Majeed score were 100% in both groups. There were no significant differences in the Matta evaluation or Majeed score between the two groups (both P > 0.05), whereas the operative time, intraoperative bleeding volume, blood transfusion volume, incision length and hospital stay were significantly less in group A (all P < 0.05). CONCLUSION: An anterior ring internal fixator system combined with sacroiliac screw fixation can effectively treat Tile C pelvic fracture, and has advantages, including minimal invasiveness, simple operation, short operative time, safe and reliable features, fewer complications, short hospital stay and a good curative effect.

Biomechanical study of Tile C3 pelvic fracture fixation using an anterior internal system combined with sacroiliac screws.

BACKGROUND: How to perform minimally-invasive surgery on Tile C pelvic fractures is very difficult, and it is also a hot topic in orthopedic trauma research. We applied minimally-invasive treatment using an anterior internal fixator combined with sacroiliac screws. OBJECTIVES: To compare the biomechanical properties of different fixation models in pelvic facture specimens, using an internal fixation system or a steel plate combined with sacroiliac screws. METHODS: Sixteen fresh adult cadaver pelvic specimens were randomly separated into four groups named A, B, C, and D. The four groups were respectively stabilized using a two-screwed, three-screwed, or four-screwed anterior internal fixator or a steel plate with sacroiliac screws. All models were tested in both standing and sitting positions. Vertical loads of 600 N were applied increasingly. Shifts of bilateral sacroiliac joints and pubis rupture were measured. RESULTS: The shifts in sacroiliac joints and pubis rupture in the standing position were all less than 3.5 mm, and the shifts in the sitting position were all less than 1 mm. In the standing position, the results of shifts in the sacroiliac joints were group C < group D < group B < group A. For comparisons between A:B and C:D, P > 0.05. For comparisons between A, B:C, and D, P < 0.05. The results of shifts in pubis ruptures were group D < group C < group B < group A. In the comparison between C:D, P > 0.05; for comparisons between A:B, A:C, A:D, B:C, and B:D, P < 0.05. In the sitting posture, the results of shifts in the sacroiliac joints were group C < group D < group B < group A, and the shifts in the pubis ruptures were group D < group C < roup B < group A. For comparison between C:D, P > 0.05. For comparisons between A:B, A:C, A:D, B:C, and B:D, P < 0.05. CONCLUSION: Use of an anterior internal fixator combined with sacroiliac screws effectively stabilized Tile C3 pelvic fractures. The stability of specimens increased as the number of screws in the internal fixator increased.

Preliminary outcomes of allograft and hydroxyapatite as substitutes for autograft in anterior cervical discectomy and fusion with self-locking standalone cages.

PURPOSE: To investigate the efficacy and safety of allograft and hydroxyapatite (HA) as substitutes for autograft in anterior cervical discectomy and fusion (ACDF). METHODS: In this study, 49 patients (80 segments) treated with ACDF were included and allocated into three groups [group A, autogenous iliac bone, n = 18; group B, allogeneic bone, n = 16; group C, HA, n = 15]. The clinical efficacy and fusion status were compared among each group. Complications were recorded in detail, and the Bazaz classification and Voice Handicap Index-10 (VHI-10) were used to detect dysphagia and dysphonia. RESULTS: Patients exhibited similar clinical efficacy among the groups during the final follow-up. All patients in groups A and B achieved fusion compared to only 73.3% of patients in group C. Groups A and B had similar fusion score, both of which greater than that of group C. No cage subsidence was observed in group A; however, 6.3% of patients in group B and 53.3% in group C had cage subsidence. Two patients in group A (11.1%) had persistent pain at the donor site. One patient in group B had dysphagia and dysphonia (6.3%), while one patient in group C had dysphonia (6.7%). CONCLUSION: In ACDF, the autogenous iliac bone was the most ideal bone graft. The allogeneic bone was an acceptable substitute but risked cage subsidence and dysphagia. HA had a much lower fusion rate and a high risk of cage subsidence. Better substitutes should be further explored for ACDF.

EF24 induces ferroptosis in osteosarcoma cells through HMOX1.

PURPOSE: EF24, a synthetic analogue of curcumin, was developed as an anti-tumor compound to induce apoptosis, inhibit proliferation and metastasis in various cancers. However, whether EF24 induces ferroptosis in osteosarcoma cells or not, and its underlying mechanism remains largely elusive. METHODS: After EF24 combining with or without other compounds treatments, mRNA expression profiles were proceeded by RNA sequencing. Cytotoxicity was measured by cell counting kit-8 assay. Cell death was quantified by flow cytometer. Gene expression was quantified by real-time PCR. Protein level was detected by western blot. Malonydialdehyde (MDA) level was measured by lipid peroxidation MDA assay kit. Reactive oxygen species (ROS) level was measured by ROS Assay Kit. Ferric ion was measured by Iron Assay kit. RESULTS: EF24 significantly induced cell death in osteosarcoma cell lines, and this effect was significantly reversed by ferrostatin-1, but not Z-VAD(Ome)-FMK, MRT68921 or necrosulfonamide. EF24 significantly increased MDA level, ROS level and intracellular ferric ion level, these effects were significantly attenuated by ferrostatin-1. EF24 upregulated HMOX1 expression in a dose dependent manner, overexpression of HMOX1 facilitated EF24 to induce ferroptosis in osteosarcoma cell lines. HMOX1 knockdown attenuated EF24-induced cytotoxicity and attenuated EF24-induced inhibition of Glutathione Peroxidase 4 (GPX4) expression. CONCLUSION: Our results showed that EF24 upregulated HMOX1 to suppress GPX4 expression to induce ferroptosis by increasing MDA level, ROS level and intracellular ferric ion level. Thus, EF24 might serve as a potential agent for the treatment of HMOX1-positive osteosarcoma patients.

In vitro and in vivo evaluation of the pH-neutral bioactive glass as high performance bone grafts.

Osteogenic and angiogenic properties are two most valued factors for bone grafting materials. Biomedical materials with synergistic promotion effects on these two properties would be highly desirable. In this study, we showed that a recently developed pH-neutral bioactive glass (PSC) possessed such characteristics. Compared to two classical biomaterials, 45S5 bioactive glass and beta-tricalcium phosphate (ß-TCP), PSC markedly improved BMSCs' proliferation, migration and mineralization as well as their osteogenic and angiogenic differentiation. In vivo, PSC showed better performance on inducing bone regeneration than both 45S5 and ß-TCP, as featured by elevated bone mineral density (BMD) and new bone areas. PSC also significantly promoted new blood vessels formation compared with those in control groups. Furthermore, we revealed that PSC induced osteogenic and angiogenic differentiation of BMSCs through the PI3K/Akt/HIF-1α pathway, which had not been reported before. This synergistic effect of the PI3K/Akt/HIF-1α pathway on osteogenesis and angiogenic differentiation of BMSCs suggested that biomedical materials may promote new bone formation through multiple signal pathways, thus shedding light on the future development of materials with better performance.

Increased Osteoblastic Cxcl9 Contributes to the Uncoupled Bone Formation and Resorption in Postmenopausal Osteoporosis.

INTRODUCTION: Estrogen deficiency leads to bone loss in postmenopausal osteoporosis, because bone formation, albeit enhanced, fails to keep pace with the stimulated osteoclastic bone resorption. The mechanism driving this uncoupling is central to the pathogenesis of postmenopausal osteoporosis, which, however, remains poorly understood. We previously found that Cxcl9 secreted by osteoblasts inhibited osteogenesis in bone, while the roles of Cxcl9 on osteoclastic bone resorption and osteoporosis are unclear. MATERIALS AND METHODS: Postmenopausal osteoporosis mouse model was established by bilateral surgical ovariectomy (OVX). In situ hybridization was performed to detect Cxcl9 mRNA expression in bone. ELISA assay was conducted to assess Cxcl9 concentrations in bone and serum. Cxcl9 activity was blocked by its neutralizing antibody. Micro-CT was performed to determine the effects of Cxcl9 neutralization on bone structure. Cell Migration and adhesion assay were conducted to evaluate the effects of Cxcl9 on osteoclast activity. TRAP staining and Western blot were performed to assess osteoclast differentiation. CXCR3 antagonist NBI-74,330 or ERK antagonist SCH772984 was administered to osteoclast to study the effects of Cxcl9 on CXCR3/ERK signaling. RESULTS: Cxcl9 was expressed and secreted increasingly in OVX mice bone. Neutralizing Cxcl9 in bone marrow prevented bone loss in the mice by facilitating bone formation as well as inhibiting bone resorption. In vitro, Cxcl9 secreted from osteoblasts facilitated osteoclast precursors adhesion, migration and their differentiation into mature osteoclasts. The positive role of osteoblastic Cxcl9 on osteoclasts was eliminated by blocking CXCR3/ERK signaling in osteoclasts. Estrogen negatively regulated Cxcl9 expression and secretion in osteoblasts, explaining the increased Cxcl9 concentration in OVX mice bone. CONCLUSION: Our study illustrates the roles of Cxcl9 in inhibiting bone formation and stimulating bone resorption in osteoporotic bone, therefore providing a possible therapeutic target to the treatment of postmenopausal osteoporosis.

Biomechanics of Anterior Ring Internal Fixation Combined with Sacroiliac Screw Fixation for Tile C3 Pelvic Fractures.

BACKGROUND Despite the development of minimally invasive techniques for pelvic fractures, performing minimally invasive surgery for Tile C3 pelvic fractures remains challenging. Thus, we propose use of anterior ring internal fixation combined with sacroiliac screw fixation for Tile C3 pelvic fractures. MATERIAL AND METHODS A normal pelvic finite element model (model 1) was established. Two-screw, three-screw, and four-screw anterior ring internal fixators and plate combined with sacroiliac screw Tile C3 pelvic fracture models (models 2, 3, 4, and 5, respectively) were also established. A vertical load of 600 N was applied on S1. The distribution of displacement and stress in the standing and sitting positions was compared. RESULTS Models 2, 3, 4, and 5 can provide effective fixation. Compared with model 1, in the erect position, the maximum displacement of models 2, 3, 4, and 5 increased by 66.51%, 65.36%, 35.16%, and 35.47% and the maximum stress increased by 201.78%, 130.65%, 100.82%, and 99.03%, respectively. Compared with model 1, in sitting position, the maximum displacement of models 2, 3, 4, and 5 increased by 9.1%, 11.04%, 5.57%, and 8.59% and the maximum stress increased by 157.73%, 118.02%, 98.32%, and 93.16%, respectively. CONCLUSIONS Anterior ring internal fixators combined with sacroiliac screws can effectively fix Tile C3 pelvic fractures.

The Anatomical Study and Clinical Significance of the Sinuvertebral Nerves at the Lumbar Levels.

STUDY DESIGN: A dissection-based study of 10 embalmed human cadavers. OBJECTIVE: The purpose of this study was to describe the sinuvertebral nerves at the lumbar level and to discuss their possible clinical significance. SUMMARY OF BACKGROUND DATA: Discogenic low-back pain is mediated by the sinuvertebral nerves. However, the detailed descriptions of the sinuvertebral nerves at the lumbar level are lacking. METHODS: One hundred L1-L5 intervertebral foramina from 10 embalmed cadavers were studied. The presence of the sinuvertebral nerves was noted. The quantity, origin, pathway, innervation range, and spatial orientations of the sinuvertebral nerves in the L1-L5 intervertebral foramina were examined. RESULTS: A total of 450 sinuvertebral nerves were identified in the 100 lumbar intervertebral foramina; sinuvertebral nerves were observed in 100.00% of the intervertebral foramina. The sinuvertebral nerves were routinely divided into the following two types: the sinuvertebral nerve deputy branch and sinuvertebral nerve main trunk. Three hundred twelve sinuvertebral nerve deputy branches were found; on average, there were approximately 3.12 (range, 1-8) branches in each intervertebral foramen. One hundred thirty-eight sinuvertebral nerve main trunks were found, and sinuvertebral nerve main trunks were observed in 97.00% of the intervertebral foramina. The initial portion of the sinuvertebral nerve was located along the posterior-lateral edge of the disc to the spinal canal. Sixty-one (44.20%) sinuvertebral nerve main trunks originated from the starting point of the gray ramus communicans of the nerve root; 77 (55.80%) sinuvertebral nerve main trunks originated from the anterior surface of the spinal ganglia of the nerve root. CONCLUSION: This is a systematic anatomy study that describes the sinuvertebral nerve at the lumbar level and may be of clinical importance to spinal surgeons. A comprehensive understanding of the distribution of sinuvertebral nerves may lead to significant benefits for patients undergoing percutaneous endoscopic treatment for discogenic low-back pain. LEVEL OF EVIDENCE: 4.

Clinical Anatomy and Possible Clinical Significance of the Postcentral Branches of Spinal Arteries in the L1-L5 Levels.

STUDY DESIGN: This was a dissection-based study of 10 embalmed human cadavers. OBJECTIVE: The objective of this study was to identify and describe the postcentral branches in the L1-L5 intervertebral foramina (IVF) and to determine their possible clinical significance. SUMMARY OF BACKGROUND DATA: The lower lumbar segmental arteries have been well studied. However, there are few articles with regard to the postcentral branches in the L1-L5 IVF. MATERIALS AND METHODS: Eighty L1-L5 IVF from 10 embalmed cadavers were studied with a surgical microscope, and the postcentral branches were identified. The branches, origin, insertion, and spatial orientation of the postcentral branches in the L1-L5 IVF were examined. The diameter of the arteries was measured using a Vernier caliper. RESULTS: In our study, the occurrence rate of a postcentral branch was 100.00% in the 80 IVFs. The postcentral branch was routinely divided into the following 2 types: type 1, postcentral branch main trunks (65.00%), which branch from the spinal arteries or lumbar arteries and then divide into 2 branches (superior and inferior branches), and type 2, superior and inferior branches, which branch straight from the spinal arteries (35.00%). The initial portion of the postcentral branches traveled around the anterolateral edge of the disk to the dorsum. CONCLUSIONS: Postcentral branches of spinal arteries are common structures in IVF; there are 2 types of postcentral branches. Thorough understanding of the spinal arteries before percutaneous endoscopic lumbar discectomy may be an important step in reducing intraoperative bleeding and ensuring clear visualization, which may result in significant benefits for patients.

[Risedronate inhibits rat bone marrow adipogenesis and reduces RANKL expression in adipocytes].

OBJECTIVE: To investigate the effects of risedronate on bone marrow adipogenesis and the expression of the receptor activator of nuclear factor κB ligand (RANKL) in adipocytes in the bone marrow micro-environment. METHODS: Primary cultured rat mesenchymal stem cells (BMSCs) with or without adipogenic induction for 14 days were treated with 1, 5, 10, and 25 µmol/L risedronate. The droplets of the differentiated adipocytes were analyzed, and Western blotting was performed to detect the expression level of RANKL. Female SD rats (24-week-old) were randomly divided into sham-operated group and ovariectomy (OVX) group, and 12 weeks after the operation, the OVX rats were further divided into control group and risedronate group (2.4 µg/kg, injected subcutaneously for 3 times a week). Eight weeks later, the bone mineral density (BMD) of the rats and bone marrow histopathology of the femurs was examined to evaluate the effect of risedronate on the fat fraction in the bone marrow. RESULTS: Risdronate significantly inhibited adipogenic differentiation of rat BMSCs and suppressed RANKL expression in the adipocytes derived from the BMSCs in a concentration-dependent manner. In OVX rats, risdronate treatment significantly increased the BMD and decreased the fat content in the bone marrow. CONCLUSIONS: Risdronate can effectively inhibit the adipogenic differentiation of rat BMSCs, decrease fat content in the bone marrow, and suppress the generation and function of osteoclasts by down-regulating the expression of RANKL, which can be an important mechanism underlying the therapeutic effect of risedronate against osteoporosis.

Orcinol glucoside facilitates the shift of MSC fate to osteoblast and prevents adipogenesis via Wnt/ß-catenin signaling pathway.

BACKGROUND: During osteoporosis, bone mesenchymal stem cells (BMSCs) lineage commitment shifts to adipocytes, causing fat accumulation and bone loss in the skeleton. Seeking drugs that could reverse the adipocyte fate determination of BMSCs is critical for osteoporosis therapy. As a traditional Chinese medicine, Rhizoma Curculiginis (Xianmao) has been used to treat bone diseases and promote bone healing, while the effective constituent of it and the underlying mechanisms are unknown. OBJECTIVES: The aim of this study is to unveil the role of orcinol glucoside (OG), one constituent of Rhizoma Curculiginis, in osteoporosis and BMSCs lineage commitment and to explore the underlying mechanisms. METHODS: Micro-CT and three-point bending test were performed to determine the effect of OG on bone structure and strength. qT-PCR and Western blot were performed to determine the expression of osteogenic or adipogenic differentiation markers in BMSCs. Mineralization in differentiated BMSCs was assessed by Alizarin Red staining, and lipid accumulation in the cells was evaluated by Oil Red O staining. All measurements were performed at least three times. RESULTS: OG prevented bone loss by stimulating bone formation and attenuating fat formation in bone. In vitro, OG promoted osteoblastic differentiation and inhibited adipogenic differentiation of BMSCs. Inhibition of Wnt/ß-catenin by ICG-001 significantly reversed the effect of OG on osteogenic and adipogenic differentiation of BMSCs. CONCLUSION: Our study demonstrated the role of OG in alleviating bone loss and fat accumulation in osteoporotic bone, therefore bringing a new therapeutic means to the treatment of osteoporosis.