Objective: Mechanisms involved in developing intervertebral disc degeneration (IDD) are poorly understood, thus making developing effective therapies difficult. This study aimed to suggest a possible molecular mechanism, based on transcriptome sequencing‐identified transforming growth factor (TGF‐β), underlying the effects on bone homeostasis in IDD.Methods: A mouse model for IDD was established. Transcriptome sequencing of nucleus pulposus tissue from mice (n = 3) identified differentially expressed mRNAs and key genes impacting bone homeostasis. A protein–protein interaction network pinpointed core genes. GO and KEGG analysis revealed gene functions. Expression levels of TGF‐β1, tartrate‐resistant acid phosphatase (TRAP), and cathepsin K (CTSK) were measured. Micro‐CT evaluated vertebral structures and vascular imaging. Western Blot measured expression levels of Vegf, Opn, MMP3, and MMP13. Safranin O‐Fast Green and TRAP staining were performed on intervertebral discs and endplates.Results: Transcriptomic analysis found 1790 differentially expressed mRNAs in IDD mice. Twenty‐eight genes related to bone homeostasis in IDD were identified. TGF‐β1 was confirmed as the core gene. GO and KEGG showed TGF‐β1 regulates osteoclast markers like CTSK and TRAP through pathways including NF‐κB and MAPK. Experimental validation revealed lower TGF‐β1 expression in IDD mice than controls, and increased TRAP and CTSK expression. Micro‐CT showed decreased bone mass and intervertebral disc space in IDD mice. Vascular imaging showed increased vascular volume in IDD cartilaginous endplates. Western blot displayed increased VEGF and OPN levels, but decreased MMP3 and MMP13 in IDD mice. Safranin O‐fast green staining revealed severe IDD degeneration. However, TGF‐β1 injection improved bone parameters in IDD mice. In vitro experiments confirmed TGF‐β1 inhibits bone marrow macrophages differentiation into osteoclasts.Conclusion: From our data, we conclude that TGF‐β1 repressed osteoclast differentiation and aberrant bone‐associated angiogenesis in cartilage endplates (EPs) to alleviate IDD, which may be instrumental for the therapeutic targeting of IDD.
Background: Picture Archiving and Communication Systems (PACS) is the gold standard for the measurement of spinal parameters. The aim of this study is to evaluate the practical value of using an iPhone to rapidly measure lumbosacral spine-pelvic sagittal parameters, and compared the measurement time and accuracy between iPhone and PACS. Methods: The study group consisted of 50 patients. They were examined with a lateral x-ray of the whole spine in a standard standing position, as well as by three-dimensional CT scan of the lumbosacral area from January to September 2016. An iPhone was employed to take and observe pictures in order to measure the extent of lumbar lordosis (LL), pelvic tilt (PT), and sacral slope (SS). We compared the results with those obtained with PACS, and analyzed the reliability and measurement errors between the two acquisition methods. Results: The average measurement values obtained with PACS were as follows: (LL): 53.56 ± 15.76°, (PT): 12.60 ± 5.15°, (SS): 42.16 ± 13.29°. The average measurement values obtained by iPhone were as follows: LL: 52.20 ± 14.46°, PT: 12.48 ± 5.39°, SS: 12.48 ± 5.39°. There was no statistical significance difference found between the values obtained using the two methods, P > 0.05. The two methods of measurement of intra-class correlation coefficients (ICCs) were 0.938(De-LL), 0.812(De-PT) and 0.946(De-SS). There was no statistically significant difference in the deviation between the two measurement methods. PACS measurement time: 18.53 ± 1.44 s; iPhone measurement time: 14.02 ± 1.08 s, iPhone demonstrating statistically significant faster measurement times than PACS, P < 0.05. Conclusion: Using the iPhone’s built-in photo editing function to rapidly measure the parameters of the spinal- pelvic sagittal plane balance in the lumbosacral region is relatively accurate and reliable. This might provide a great convenience for Orthopedists in their clinical works, because they can measure imaging pictures with their iPhones at any time and place.
Background: Intervertebral disc degeneration (IDD) is a major contributor to low back pain, yet its molecular mechanisms remain unclear. Identifying potential druggable genes (PDGs) associated with IDD could facilitate early diagnosis and targeted therapy. This study aimed to explore the diagnostic and mechanistic significance of PDGs in IDD. Methods and Results: Three GEO datasets were merged as a training set, with another blood-based dataset as testing. PDGs were obtained from the literature and intersected with differentially expressed genes (DEGs). Functional enrichment and immune infiltration analyses were performed. A Lasso regression model was developed for diagnosis, and Mendelian Randomization (MR) analysis inferred causality. Cellular experiments validated key gene expression. Fourteen differentially expressed PDGs were identified, primarily involved in immune responses and neutrophil activity. A five-gene diagnostic model (BPI, CD160, CTSG, CYP27A1, KIF11) was constructed and demonstrated high accuracy. MR analysis confirmed a causal relationship between BPI and CTSG with IDD. GSEA revealed that BPI was negatively associated with oxidative phosphorylation, while CTSG was linked to the G2M checkpoint. Cellular experiments confirmed BPI and CTSG upregulation in TNF-α-induced NPCs. Conclusion: This study constructed a diagnostic model and identified BPI and CTSG as potential biomarkers for IDD, providing new insights into IDD treatment.