These authors contributed equally to this work. Keywords: MicroRNA, osteoclast, osteoporosisAbbreviations: GM-CSF, Granulocyte macrophage colony-stimulating factor; MiRNA, microRNA; 3'-UTR; 3' untranslated region; BMMs, bone marrow macrophages; PDCD4, programmed cell death 4; FasL, Fas ligand; PIO, particle-induced osteolysis; Calcr, calcitonin receptor; RDX, radixin; M-RIP, myosin phosphatase-Rho interacting protein; ITGA5, integrin a5; Fzd3, frizzled 3; ALP, alkaline phosphatase; TRAP, tartrate-resistant acid phosphatase; CXCL11, chemokine (C-X-C motif) ligand 11; CXCR3, chemokine (C-X-C motif) receptor 3; SLC39A1, solute carrier family (zinc transporter) member 1; TRAF6, TNF receptor-associated factor 6; OVX, ovariectomy; MAFB, V-maf musculoaponeurotic fibrosarcoma oncogene homolog B; CBL, Casitas B-lineage lymphoma proto-oncogene; PAG1, phosphoprotein associated with glycosphingolipid microdomains; TOB2, transducer of ERBB2; sICAM1, soluble intracellular adhesion molecule.Osteoclasts are the exclusive cells of bone resorption. Abnormally activating osteoclasts can lead to low bone mineral density, which will cause osteopenia, osteoporosis, and other bone disorders. To date, the mechanism of how osteoclast precursors differentiate into mature osteoclasts remains elusive. MicroRNAs (miRNAs) are novel regulatory factors that play an important role in numerous cellular processes, including cell differentiation and apoptosis, by post-transcriptional regulation of genes. Recently, a number of studies have revealed that miRNAs participate in bone homeostasis, including osteoclastic bone resorption, which sheds light on the mechanisms underlying osteoclast differentiation. In this review, we highlight the miRNAs involved in regulating osteoclast differentiation and bone resorption, and their roles in osteoporosis.

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Osteoporosis is characterized by a decrease in bone mass and strength, rendering people prone to osteoporotic fractures caused by low-energy forces. The primary treatment strategy for osteoporotic fractures is surgery; however, the compromised and comminuted bones in osteoporotic fracture sites are not conducive to optimum reduction and rigid fixation. In addition, these patients always exhibit accompanying aging-related disorders, including high inflammatory status, decreased mechanical loading and abnormal skeletal metabolism, which are disadvantages for fracture healing around sites that have undergone orthopedic procedures. Since the incidence of osteoporosis is expected to increase worldwide, orthopedic surgeons should pay more attention to comprehensive strategies for improving the poor prognosis of osteoporotic fractures. Herein, we highlight the molecular basis of osteoimmunology and bone mechanosensation in different healing phases of elderly osteoporotic fractures, guiding perioperative management to alleviate the unfavorable effects of insufficient mechanical loading, high inflammatory levels and pathogen infection. The well-informed pharmacologic and surgical intervention, including treatment with anti-inflammatory drugs and sufficient application of antibiotics, as well as bench-to-bedside strategies for bone augmentation and hardware selection, should be made according to a comprehensive understanding of bone biomechanical properties in addition to the remodeling status of osteoporotic bones, which is necessary for creating proper biological and mechanical environments for bone union and remodeling. Multidisciplinary collaboration will facilitate the improvement of overall osteoporotic care and reduction of secondary fracture incidence.

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Previous studies showed that some patients after the treatment of anti-programmed cell death protein-1 (anti-PD-1) antibodies experienced immune-related diarrhea. In this study, we aim to explore the association between intestinal microbiota and immune-related diarrhea. Methods: We obtained the fecal samples of 26 advanced lung cancer patients before the first dose of anti-PD-1 antibodies. Results: Eight of 26 patients experienced diarrhea after the treatment of anti-PD-1 antibodies. At the phylum level, our study demonstrated that Bacteroidetes were higher in diarrhea-free (D-F) patients, while Firmicutes were lower. Bacteroides and Parabacteroides belonging to Bacteroidetes phylum and Phascolarctobacterium of Firmicutes phylum were more abundant in D-F patients. Whereas, Veillonella of Proteobacteria phylum was lower in D-F patients. Conclusion: Our study highlights that intestinal microbiota variation is correlated with the subsequent development of immune-related diarrhea.