Radiographic patterns and characteristics of sagittal profiles in normal spinopelvic curvatures: An explicit depiction of the distribution of lumbar vertebral bodies and discs.

The current study aimed to investigate the sagittal morphology of the spinopelvic complex and the components of the lumbar spine in the normal population. In total, 132 adult volunteers were retrospectively evaluated and divided into four groups according to the Roussouly classification. Statistical analysis of radiological parameters, including lumbar lordosis (LL), thoracic kyphosis (TK), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), PI-LL, LL-TK, lumbar vertebral lordosis from L1 to L5 (L1L-L5L), the intervertebral angle from L1-L2 to L5-S1 (IVA1-2-IVA5-1), segmental lordosis from L1 to L5 (S1L-S5L), the proportion of L1-L5 (L1%-L5%), the proportion of the intervertebral angle from L1-L2 to L5-S1 (IVA1-2%-IVA5-1%), and proportion of segmental lordosis from L1 to L5 (S1L%-S5L%), was performed. Based on the classification, type II (n = 46) was the most common, followed by type I (n = 39), type III (n = 36), and type IV (n = 11). The quantitative values of the sagittal parameters of the four groups were obtained. Results showed a significant difference in terms of LL, PI, SS, and LL-TK. Further, L1%, L2%, L3%, IVA1-2%, IVA2-3%, S1L%, S2L%, and S3L% had an increasing trend. PI was positively correlated with LL, S1L, S2L, S3L, S4L, S1L%, and S2L%, but not with S5L%. In conclusion, pelvic parameters had a significant effect on lumbar curvature and lordosis distribution. Further, the abovementioned results were beneficial for individual surgical decision-making regarding targeted intervertebral angle, screw-insertion dimension, and rod contouring.

Association between serum levels of bone turnover markers and bone mineral density in men and women with type 2 diabetes mellitus.

BACKGROUND: In patients with type 2 diabetes mellitus (T2DM), higher risks of impaired bone metabolism are widely reported. To evaluate bone metabolism, bone mineral density (BMD) and bone turnover levels should be included. In this article, we analyzed the relationship between them in T2DM. METHODS: We conducted a hospital-based cross-sectional study enrolling 1499 patients hospitalized for T2DM between October 2009 and January 2013. Multivariate linear regression models were used to identify the relationship between bone turnover markers (BTMs) and BMD levels. A two-sided P-value < .05 was considered statistically significant. RESULTS: After adjusting for confounding factors, osteocalcin (OC) showed a negative relationship with total lumbar, femur neck, and total hip BMD in men and women. N-terminal propeptides of type I collagen (P1NP) and alkaline phosphatase (ALP) showed a negative association with BMD at three sites in men and total lumbar BMD in women, whereas in the femur neck and total hip in women, the relationship was only found for P1NP with total hip. For ß-C-terminal telopeptides of type I collagen (ß-CTX), a negative relationship was also found in all three sites for BMD in men and total lumbar BMD in women, whereas ß-CTX was not associated in the femoral neck and total hip in women. CONCLUSION: In patients with T2DM, serum levels of OC, P1NP, ß-CTX, and ALP were negatively correlated with BMD levels in men in three sites and with total lumbar BMD in women. The relationship varied in femur neck and total hip BMD in women.

Pilose antler peptide potentiates osteoblast differentiation and inhibits osteoclastogenesis via manipulating the NF-κB pathway.

Bones are inflexible yet ever-changing metabolic organs, and bone homeostasis is maintained through two delicately regulated processes: bone construction and bone reabsorption. An imbalance in bone metabolism is linked to most orthopedic diseases, including osteoporosis and rheumatoid arthritis. Importantly, tumor necrosis factor-α (TNF-α) blocks osteoblast differentiation and stimulates osteoclast formation, resulting in delayed deposition of new bone and accelerated bone resorption, especially in rheumatoid arthritis patients with inflammatory conditions. Pilose antler peptide (PAP) isolated and purified from deer antlers has been shown to have beneficial effects on chronic inflammation. In the present study, we studied the impact of PAP on osteoblast differentiation and evaluated the regulatory mechanism, with particular emphasis on the effect of PAP on TNF-α-mediated NF-κB signaling. Mouse primary osteoblast cells were activated with bone morphogenetic protein-2 (BMP-2) for osteoblast differentiation. A significant stimulatory effect of PAP in osteoblastogenesis was observed using ALP activity and Alizarin Red S staining assays. Meanwhile, PAP significantly rescued TNF-α-induced impairment of osteoblast formation as well as mineralization. Furthermore, we found a similar trend upon analyzing osteoblast-specific gene expression. PAP significantly rescued TNF-α-mediated decrease in expression of osteoblast-specific genes. A molecular mechanism assay indicated that PAP significantly inhibited TNF-α-mediated stimulation of NF-κB signaling activity, as well as nuclear translocation of its subunit p65. Moreover, over-expression of p65 reversed the stimulatory effects of PAP on osteoblast differentiation. Furthermore, we also identified that PAP dose dependently inhibit osteoclastogenesis, and this effect might be achieved via suppressing NF-κB activity. In summary, this study shows that PAP promotes osteoblast differentiation and blocks TNF-α-mediated suppression of osteoblastogenesis in vitro via the NF-κB/p65 pathway, as well as inhibits osteoclastsogenesis in vitro. Therefore, PAP, a novel drug with both antiresorptive and osteoanabolic activity, shows therapeutic potential as an alternative treatment for osteolytic diseases, including rheumatoid arthritis and osteoporosis.

Upregulation of P63 inhibits chondrocyte autophagy thereby enhancing the malignant progression of osteoarthritis.

Loss of autophagy is suggested to play a key role in the progression of osteoarthritis (OA). P63 is a member of the P53 family, which is widely dysregulated in various tumors. However, the specific role of P63 in chondrocyte autophagy has never been fully understood. Here, the expression level of P63 in the articular cartilages of OA patients and chondrocytes treated with 3-MA was explored using western blot. Autophagy was determined using transmission electron microscopy and mRFP-GFP-LC3 assay. Fewer autophagic vesicles were identified in the articular cartilages of OA patients compared with that of normal control. Both the mRNA and protein levels of P63 was markedly increased in the articular cartilages of OA patients compared with that of normal control. MTT assay demonstrated that P63 overexpression markedly reduced chondrocyte viability at 24, 36 and 48 h, while inhibition of P63 inhibited cell viability at 24, 36 and 48 h, respectively. Furthermore, autophagic flux assay showed that transfection of ad-P63 markedly decreased the yellow dots in chondrocytes, while inhibition of P63 induced chondrycyte autophagy. In summary, we first demonstrated that upregulation of P63 in the cartilage tissues of OA patients inhibited chondrocyte autophagy thereby contributing to the malignant progression of OA.

Macrophages derived from THP-1 promote the osteogenic differentiation of mesenchymal stem cells through the IL-23/IL-23R/ß-catenin pathway.

Abnormal bone formation is a clinically significant dilemma for many conditions in response to injury, inflammation or genetic disease. However, the effects of inflammation on the osteogenic differentiation of mesenchymal stem cells (MSCs) remain unclear. IL-23 secretion from macrophages might contribute to the development of bone formation. Here, we investigated the stimulatory effects of THP-1 macrophage conditioned medium (MΦ CM) on the osteogenic differentiation of human MSCs and the associated signaling pathways. The osteogenic differentiation of MSCs was induced after exposure to osteogenic differentiation medium (OM). MΦ CM significantly increased alkaline phosphate (ALP) activity and calcium mineralization in MSCs. Osteogenic marker genes, including RUNX2, ALP and osteocalcin (OCN), were also up-regulated in MSCs after exposure to MΦ CM. Moreover, western blotting revealed that MΦ CM treatment induced STAT3 and ß-catenin activation in MSCs. Furthermore, blockade of IL-23 in MΦ CM not only impaired the osteogenic-promotion effects of macrophage but also decreased the expression of osteogenic maker genes. However, IL-23R silencing suppressed MΦ CM-induced calcium mineralization and osteogenic maker gene expression in MSCs. These data suggest that macrophages derived from THP-1 promote the osteoblastic differentiation of MSCs through the IL-23/IL-23R/ß-catenin pathway and macrophages might contribute to the development of bone formation in inflammation.

[A comparison of results between percutaneous transforaminal endoscopic discectomy and fenestration discectomy for lumbar disc herniation in the adolscents].

OBJECTIVE: To compare the preliminary clinical outcomes of percutaneous transforaminal endoscopic discectomy (PTED) and fenestration discectomy (FD) for lumbar disc herniation in the adolscents and further to summarize the clinical experience. METHODS: The data of 56 patients with single segment lumbar disc herniation who were adopted by our department from January 2011 to December 2013 were retrospectively studied. All patients were divided into 2 groups, including 30 patients undergoing PTED and 26 patients undergoing FD respectively. The factors including the length of skin incision, amount of intraoperative bleeding, operation time and duration of hospitalization were compared. Pfirrmann grading system was used for assessment of lumbar disc degeneration preoperatively and 1 year later. The visual analogue scale (VAS), Oswestry Disability Index (ODI) and Japanese Orthopedic Association (JOA) scores were used to measure the clinical outcomes. RESULTS: There were significant differences in the observation factors such as the skin incision length, amount of intraoperative bleeding, operation time and duration of hospitalization between the PTED and FD groups (P < 0.05). After surgery, the patients in both groups were followed up for 12 months on average respectively. The postoperative lumbar disc degeneration in PTED group was decreased than that of in FD group. The postoperative VAS scores, ODI and JOA scores at each follow-up time point in both groups were significantly improved when compared with the preoperative ones (P < 0.05). There were no statistically significant differences between the 2 groups in the JOA score improvement rate (P > 0.05). According to 'the modified MacNab criteria, there were no statistically significant differences between the 2 groups in the excellent and good rate (P > 0.05). CONCLUSIONS: The preliminary clinical efficacy of both PTED and FD in the treatment of single segment lumbar disc herniation in the adolscents is satisfactory. However, PTED is a better minimally invasive surgical method with such advantages as less trauma, less blood loss, early function recovery, less effect on lumbar spinal stability and so on. The short-term outcomes of PTED are similar to that of FD.

[Full-endoscopic interlaminar approach discectomy for central lumbar disc extrusion].

OBJECTIVE: To evaluate the safety and efficacy of percutaneous endoscopic lumbar discectomy (PELD) in the treatment of central lumbar disc extrusion via an interlaminar approach. METHODS: Between January 2012 and January 2014, 27 low-back pain patients with radicular central lumbar disc herniations underwent percutaneous endoscopic discectomy through an interlaminar approach. The clinical follow-ups were performed at 3 months, 6 months and 1 year with an extensive postoperative questionnaire, including pain visual analog scale (VAS) and Oswestry disability index (ODI). RESULTS: Mini-invasive operation was completed successfully in all patients. The mean operative duration was 41 (26-83) min and the average postoperative hospitalization time 5 (2-7) days. The postoperative median VAS and ODI scores significant decreased at all time-points. Twenty-five patients had no longer leg pain. But the recurrence rate of disc herniation stood at 7.4%. One patient undergo reoperation (microscopic discectomy) and another showed a significant relief in pain symptoms after conservative treatment. CONCLUSION: Endoscopic discectomy via an interlaminar approach for central lumbar disc extrusion offers significant advantages of faciliating rehabilitation, reducing complications, minimizing trauma and lowering expenditure.

Antibacterial properties of magnesium in vitro and in an in vivo model of implant-associated methicillin-resistant Staphylococcus aureus infection.

Periprosthetic infection remains a challenging clinical complication. We investigated the antibacterial properties of pure (99.9%) magnesium (Mg) in vitro and in an in vivo rat model of implant-related infection. Mg was highly effective against methicillin-resistant Staphylococcus aureus-induced osteomyelitis and improved new peri-implant bone formation. Bacterial icaA and agr RNAIII transcription levels were also assessed to characterize the mechanism underlying the antibacterial properties of the Mg implant.

Dioscin inhibits osteoclast differentiation and bone resorption though down-regulating the Akt signaling cascades.

Bone resorption is the unique function of osteoclasts (OCs) and is critical for both bone homeostasis and pathologic bone diseases including osteoporosis, rheumatoid arthritis and tumor bone metastasis. Thus, searching for natural compounds that may suppress osteoclast formation and/or function is promising for the treatment of osteoclast-related diseases. In this study, we for the first time demonstrated that dioscin suppressed RANKL-mediated osteoclast differentiation and bone resorption in vitro in a dose-dependent manner. The suppressive effect of dioscin is supported by the reduced expression of osteoclast-specific markers. Further molecular analysis revealed that dioscin abrogated AKT phosphorylation, which subsequently impaired RANKL-induced nuclear factor-kappaB (NF-κB) signaling pathway and inhibited NFATc1 transcriptional activity. Moreover, in vivo studies further verified the bone protection activity of dioscin in osteolytic animal model. Together our data demonstrate that dioscin suppressed RANKL-induced osteoclast formation and function through Akt signaling cascades. Therefore, dioscin is a potential natural agent for the treatment of osteoclast-related diseases.

Andrographolide prevents human breast cancer-induced osteoclastic bone loss via attenuated RANKL signaling.

Bone metastasis is a common and serious complication in advanced cancers such as breast cancer, prostate cancer, and multiple myeloma. Agents that prevent bone loss could be used to develop an alternative therapy for bone metastasis. RANKL, a member of the tumor necrosis factor superfamily, has been shown to play a significant role in cancer-associated bone loss. In this study, we examined the efficacy of the natural compound andrographolide (AP), a diterpenoid lactone isolated from the traditional Chinese and Indian medicinal plant Andrographis paniculata, in reducing breast cancer-induced osteolysis. AP prevented human breast cancer-induced bone loss by suppressing RANKL-mediated and human breast cancer cell-induced osteoclast differentiation. Molecular analysis revealed that AP prevented osteoclast function by inhibiting RANKL-induced NF-κB and ERK signaling pathway in lower dose (20 µM), as well as inducing apoptosis at higher dose (40 µM). Thus, AP is a potent inhibitor of breast cancer-induced bone metastasis.

Meta-analysis of sonication fluid samples from prosthetic components for diagnosis of infection after total joint arthroplasty.

This meta-analysis included 12 studies that evaluated sonication fluid cultures (SFC) for the diagnosis of prosthetic joint infection (PJI). The pooled sensitivity and specificity were 0.80 (95% confidence interval [CI], 0.74 to 0.84) and 0.95 (CI, 0.90 to 0.98), respectively. Subgroup analyses showed that a 14-day anaerobic culture may improve sensitivity, the use of centrifugation or vortexing may improve specificity, and the use of 400 to 500 ml of Ringer's solution for containers may improve sensitivity and specificity. The best SFC cutoff was ≥5 CFU. In conclusion, SFC has high sensitivity and very high specificity for diagnosing PJI.

A Multi-Element Identification System Based on Deep Learning for the Visual Field of Percutaneous Endoscopic Spine Surgery.

Background: Lumbar disc herniation is a common degenerative lumbar disease with an increasing incidence. Percutaneous endoscopic lumbar discectomy can treat lumbar disc herniation safely and effectively with a minimally invasive procedure. However, the learning curve of this technology is steep, which means that initial learners are often not sufficiently proficient in endoscopic operations, which can easily lead to iatrogenic damage. At present, the application of computer deep learning technology to clinical diagnosis, treatment, and surgical navigation has achieved satisfactory results. Purpose: The objective of our team is to develop a multi-element identification system for the visual field of endoscopic spine surgery using deep learning algorithms and to evaluate the feasibility of this system. Method: We established an image database by collecting surgical videos of 48 patients diagnosed with lumbar disc herniation, which was labeled by two spinal surgeons. We selected 6000 images of the visual field of percutaneous endoscopic spine surgery (including various tissue structures and surgical instruments), divided into the training data, validation data, and test data according to 2:1:2. We developed convolutional neural network models based on instance segmentation-Solov2, CondInst, Mask R-CNN and Yolact, and set the four network model backbone as ResNet101 and ResNet50 respectively. Mean average precision (mAP) and frames per second (FPS) were used to measure the performance of each model for classification, localization and recognition in real time, and AP (average) is used to evaluate how easily an element is detected by neural networks based on computer deep learning. Result: Comprehensively comparing mAP and FSP of each model for bounding box test and segmentation task for the test set of images, we found that Solov2 (ResNet101) (mAP = 73.5%, FPS = 28.9), Mask R-CNN (ResNet101) (mAP = 72.8%, FPS = 28.5) models are the most stable, with higher precision and faster image processing speed. Combining the average precision of the elements in the bounding box test and segmentation tasks in each network, the AP(average) was highest for tool 3 (bbox-0.85, segm-0.89) and lowest for tool 5 (bbox-0.63, segm-0.72) in the instrumentation, whereas in the anatomical tissue elements, the fibrosus annulus (bbox-0.68, segm-0.69) and ligamentum flavum (bbox-0.65, segm-0.62) had higher AP(average),while extra-dural fat (bbox-0.42, segm-0.44) was lowest. Conclusion: Our team has developed a multi-element identification system for the visual field of percutaneous endoscopic spine surgery adapted to the interlaminar and foraminal approaches, which can identify and track anatomical tissue (nerve, ligamentum flavum, nucleus pulposus, etc.) and surgical instruments (endoscopic forceps, an high-speed diamond burr, etc.), which can be used in the future as a virtual educational tool or applied to the intraoperative real-time assistance system for spinal endoscopic operation.

Postoperative MRI Findings Following PELD and Their Correlations with Clinical Prognosis are Investigated by Injecting Contrast into Annulus Fibrosus Intraoperatively.

Objective: To validate whether a residual mass demonstrated on early postoperative MR after percutaneous endoscopic lumbar discectomy (PELD) is indeed an intraoperatively retained annulus fibrosus, and explore the correlation between imaging changes in the residual mass and clinical prognosis of patients. Methods: A prospective study of 118 patients were included. During surgery, a contrast medium, Gadopentetate Dimeglumine, was injected around the ruptured annulus fibrosus. The intensity of the T2 signal, the size of the remaining mass (SR), and the cross-sectional area of the spinal canal (SCSA), VAS, and ODI were assessed at preoperative, 1-h (7-day), 6-month, and 12-month postoperative intervals. Based on VAS at 7 days post-surgery, patients were classified into either a non-remission group (Group A, VAS > 3) or a remission group (Group B, VAS ≤ 3). Results: Six patients who developed recurrent LDH were excluded. A residual mass was detected on MRI 1 h after surgery in 94.6% (106/112). During one year of follow-up, 90.1% (101/112) of the patients displayed fibrous annulus remodeling, although 68.7% (77/112) still exhibited herniation. Significant differences were found in the ODI between Groups A and B one week after surgery (p < 0.001). However, no significant differences were observed in T2 signal intensity, SR, and SCSA at 1-h, 6-month and 12-month post-surgery (p > 0.05) between the two groups. In a multiple linear regression analysis, early postoperative ODI changes were associated with T2 signal (B = -10.22, sig < 0.05), long-term changes were associated with alterations in SR (B = 5.63, sig < 0.05) and SCSA (B = -0.13, sig < 0.05). Conclusion: The residual mass observed in early postoperative MR images after PELD was the retained annulus fibrosus intraoperatively. Short-term changes in clinical symptoms after PELD were linked to T2 signal intensity, while long-term changes were associated with changes in SR and SCSA.

Sanguinarine inhibits osteoclast formation and bone resorption via suppressing RANKL-induced activation of NF-κB and ERK signaling pathways.

Sanguinarine is a natural plant extract that has been supplemented in a number of gingival health products to suppress the growth of dental plaque. However, whether sanguinarine has any effect on teeth and alveolar bone health is still unclear. In this study, we demonstrated for the first time that sanguinarine could suppress osteoclastic bone resorption and osteoclast formation in a dose-dependent manner. Sanguinarine diminished the expression of osteoclast marker genes, including TRAP, cathepsin K, calcitonin receptor, DC-STAMP, V-ATPase d2, NFATc1 and c-fos. Further investigation revealed that sanguinarine attenuated RANKL-mediated IκBα phosphorylation and degradation, leading to the impairment of NF-κB signaling pathway during osteoclast differentiation. In addition, sanguinarine also affected the ERK signaling pathway by inhibiting RANKL-induced ERK phosphorylation. Collectively, this study suggested that sanguinarine has protective effects on teeth and alveolar bone health.

Bone mineral density and risk of breast cancer in postmenopausal women.

High bone mineral density (BMD) has been associated with increased breast cancer in prospective studies of postmenopausal women, but the real relationship is still controversial. Therefore, we undertook a meta-analysis to evaluate the association between BMD and the risk of breast cancer in postmenopausal women. We performed systematic searches on MEDLINE, EMBASE, and OVID. Data extraction was performed independently by two reviewers. For each study, we extracted the relative risks (RRs) and 95 % confidence intervals (CIs) for categorical variables and per standard deviation (SD) increases in BMD. Heterogeneity, publication bias, and subgroup analysis were performed. The analysis included 70,878 postmenopausal women from 10 studies with 1,889 breast cancers during a mean follow-up of 6 years (range 3.2-8.4 years). The summary RRs for the highest versus lowest categorical variable showed that higher BMD in the hip (RR 1.62; 95 % CI: 1.17-2.06) and in the spine (RR 1.82; 95 % CI: 1.07-2.57) were associated with a 62 and 82 % increased risk of breast cancer. Per SD, increase in hip BMD and spine BMD were also associated with a higher risk of breast cancer (RR for hip BMD 1.20; 95 % CI: 1.09-1.31 and RR for spine BMD 1.26; 95 % CI: 1.10-1.41). In this meta-analysis, a higher BMD was found to be associated with a significantly higher risk of breast cancer in postmenopausal women.

PCR-based diagnosis of prosthetic joint infection.

We performed a meta-analysis to evaluate use of PCR assays for diagnosis of prosthetic joint infection (PJI). The pooled sensitivity and specificity were 0.86 (95% confidence interval [CI], 0.77 to 0.92) and 0.91 (CI, 0.81 to 0.96), respectively. Subgroup analyses showed that use of tissue samples may improve sensitivity, and quantitative PCR and sonication of prostheses fluid may improve specificity. The results showed that PCR is reliable and accurate for detection of PJI.

Preoperative aspiration culture for preoperative diagnosis of infection in total hip or knee arthroplasty.

This meta-analysis evaluated preoperative aspiration culture for diagnosing prosthetic joint infection (PJI) in total hip arthroplasty (THA) and total knee arthroplasty (TKA). The pooled sensitivity and specificity were 0.72 (95% confidence interval, 0.65 to 0.78) and 0.95 (0.93 to 0.97), respectively. Subgroup analyses revealed nonsignificant worse diagnostic performance for THA than for TKA (sensitivity, 0.70 versus 0.78; specificity, 0.94 versus 0.96). Preoperative aspiration culture has moderate to high sensitivity and very high specificity for diagnosing PJI.

Strontium ranelate reduces cartilage degeneration and subchondral bone remodeling in rat osteoarthritis model.

AIM: To investigate whether strontium ranelate (SR), a new antiosteoporotic agent, could attenuate cartilage degeneration and subchondral bone remodeling in osteoarthritis (OA). METHODS: Medial meniscal tear (MMT) operation was performed in adult SD rats to induce OA. SR (625 or 1800 mg·kg(-1)·d(-1)) was administered via gavage for 3 or 6 weeks. After the animals were sacrificed, articular cartilage degeneration was evaluated using toluidine blue O staining, SOX9 immunohistochemistry and TUNEL assay. The changes in microarchitecture indices and tissue mineral density (TMD), chemical composition (mineral-to-collagen ratio), and intrinsic mechanical properties of the subchondral bones were measured using micro-CT scanning, confocal Raman microspectroscopy and nanoindentation testing, respectively. RESULTS: The high-dose SR significantly attenuated cartilage matrix and chondrocyte loss at 6 weeks, and decreased chondrocyte apoptosis, improved the expression of SOX9, a critical transcription factor responsible for the expression of anabolic genes type II collagen and aggrecan, at both 3 and 6 weeks. Meanwhile, the high-dose SR also significantly attenuated the subchondral bone remodeling at both 3 and 6 weeks, as shown by the improved microarchitecture indices, TMD, mineral-to-collagen ratio and intrinsic mechanical properties. In contrast, the low-dose SR did not significantly change all the detection indices of cartilage and bone at both 3 and 6 weeks. CONCLUSION: The high-dose SR treatment can reduce articular cartilage degeneration and subchondral bone remodeling in the rat MMT model of OA.

CCL3 in the bone marrow microenvironment causes bone loss and bone marrow adiposity in aged mice.

The central physiological role of the bone marrow renders bone marrow stromal cells (BMSCs) particularly sensitive to aging. With bone aging, BMSCs acquire a differentiation potential bias in favor of adipogenesis over osteogenesis, and the underlying molecular mechanisms remain unclear. Herein, we investigated the factors underlying age-related changes in the bone marrow and their roles in BMSCs' differentiation. Antibody array revealed that CC chemokine ligand 3 (CCL3) accumulation occurred in the serum of naturally aged mice along with bone aging phenotypes, including bone loss, bone marrow adiposity, and imbalanced BMSC differentiation. In vivo Ccl3 deletion could rescue these phenotypes in aged mice. CCL3 improved the adipogenic differentiation potential of BMSCs, with a positive feedback loop between CCL3 and C/EBPα. CCL3 activated C/EBPα expression via STAT3, while C/EBPα activated CCL3 expression through direct promoter binding, facilitated by DNA hypomethylation. Moreover, CCL3 inhibited BMSCs' osteogenic differentiation potential by blocking ß-catenin activity mediated by ERK-activated Dickkopf-related protein 1 upregulation. Blocking CCL3 in vivo via neutralizing antibodies ameliorated trabecular bone loss and bone marrow adiposity in aged mice. This study provides insights regarding age-related bone loss and bone marrow adiposity pathogenesis and lays a foundation for the identification of new targets for senile osteoporosis treatment.