Heterogeneous osteoimmune profiles via single-cell transcriptomics in osteoporotic patients who fail bisphosphonate treatment.

Postmenopausal osteoporosis arises from imbalanced osteoclast and osteoblast activity, and mounting evidence suggests a role for the osteoimmune system in bone homeostasis. Bisphosphonate (BP) is an antiresorptive agent, but its treatment failure rate can be as high as 40%. Here, we performed single-cell RNA sequencing on peripheral immune cells from carefully selected postmenopausal women: non-osteoporotic, osteoporosis improved after BP treatment, and BP-failed cases. We found an increase in myeloid cells in patients with osteoporosis (specifically, T cell receptor+ macrophages). Furthermore, lymphoid lineage cells varied significantly, notably elevated natural killer cells (NKs) in the BP-failed group. Moreover, we provide fruitful lists of biomarkers within the immune cells that exhibit condition-dependent differences. The existence of osteoporotic- and BP-failure-specific cellular information flows was revealed by cell-cell interaction analysis. These findings deepen our insight of the osteoporosis pathology enhancing comprehension of the role of immune heterogeneity in postmenopausal osteoporosis and BP treatment failure.

Osteobiologies for Spinal Fusion from Biological Mechanisms to Clinical Applications: A Narrative Review.

Degenerative lumbar spinal disease (DLSD), including spondylolisthesis and spinal stenosis, is increasing due to the aging population. Along with the disease severity, lumbar interbody fusion (LIF) is a mainstay of surgical treatment through decompression, the restoration of intervertebral heights, and the stabilization of motion segments. Currently, pseudoarthrosis after LIF is an important and unsolved issue, which is closely related to osteobiologies. Of the many signaling pathways, the bone morphogenetic protein (BMP) signaling pathway contributes to osteoblast differentiation, which is generally regulated by SMAD proteins as common in the TGF-ß superfamily. BMP-2 and -4 are also inter-connected with Wnt/ß-catenin, Notch, and FGF signaling pathways. With the potent potential for osteoinduction in BMP-2 and -4, the combination of allogenous bone and recombinant human BMPs (rhBMPs) is currently an ideal fusion material, which has equalized or improved fusion rates compared to traditional materials. However, safety issues in the dosage of BMP remain, so overcoming current limitations will provide significant advancement in spine surgery. In the future, translational research and the application of clinical study will be important to overcome the current limitations of spinal surgery.

Platycodi Radix Extract Prevents Hepatic Steatosis by Enhancing Bile Acid Synthesis in a High-Fat Diet-Induced Fatty Liver Mouse Model.

We aimed to identify the mechanism underlying the preventive effects of non-alcoholic fatty liver disease (NAFLD) through Platycodi Radix consumption using liver proteomic and bioinformatic analysis. C57BL/6J mice were categorized into three groups: those receiving a standard chow diet (NCD), those on a high-fat diet (HFD), and those on an HFD supplemented with 5% Platycodi Radix extract (PRE). After a 12-week period, PRE-fed mice exhibited a noteworthy prevention of hepatic steatosis. Protein identification and quantification in liver samples were conducted using LC-MS/MS. The identified proteins were analyzed through Ingenuity Pathway Analysis software, revealing a decrease in proteins associated with FXR/RXR activation and a concurrent increase in cholesterol biosynthesis proteins in the PRE-treated mouse liver. Subsequent network analysis predicted enhanced bile acid synthesis from these proteins. Indeed, the quantity of bile acids, which was reduced in HFD conditions, increased in the PRE group, accompanied by an elevation in the expression of synthesis-related proteins. Our findings suggest that the beneficial effects of PRE in preventing hepatic steatosis may be mediated, at least in part, through the modulation of FXR/RXR activation, cholesterol biosynthesis, and bile acid synthesis pathways.