LL-37 and bisphosphonate co-delivery 3D-scaffold with antimicrobial and antiresorptive activities for bone regeneration.

This study introduces a novel 3D scaffold for bone regeneration, composed of silk fibroin, chitosan, nano-hydroxyapatite, LL-37 antimicrobial peptide, and pamidronate. The scaffold addresses a critical need in bone tissue engineering by simultaneously combating bone infections and promoting bone growth. LL-37 was incorporated for its broad-spectrum antimicrobial properties, while pamidronate was included to inhibit bone resorption.

Gold nanoparticles exhibit anti-osteoarthritic effects via modulating interaction of the "microbiota-gut-joint" axis.

Osteoarthritis (OA) is a common degenerative joint disease that can cause severe pain, motor dysfunction, and even disability. A growing body of research indicates that gut microbiota and their associated metabolites are key players in maintaining bone health and in the progression of OA. Short-chain fatty acids (SCFAs) are a series of active metabolites that widely participate in bone homeostasis.

Replenishing decoy extracellular vesicles inhibits phenotype remodeling of tissue-resident cells in inflammation-driven arthritis.

The interleukin 6 (IL6) signaling pathway plays pleiotropic roles in regulating the inflammatory milieu that contributes to arthritis development. Here, we show that activation of IL6 trans-signaling induces phenotypic transitions in tissue-resident cells toward an inflammatory state. The establishment of arthritis increases the serum number of extracellular vesicles (EVs), while these EVs express more IL6 signal transducer (IL6ST, also known as gp130) on their surface.

The age-related characteristics in bone microarchitecture, osteoclast distribution pattern, functional and transcriptomic alterations of BMSCs in mice.

Deteriorated age-related bone loss is the hallmarks of skeletal aging. However, how the aging of bone marrow mesenchymal stem cells (BMSCs) and osteoclasts are linked to the bone microstructure degeneration is not yet very clear. In this study, the characteristics of age-related bone loss, distribution patterns of osteoclasts, functional and transcriptomic alterations of BMSCs, hub genes responsible for BMSCs senescence, were analyzed.

Bile acid metabolism regulatory network orchestrates bone homeostasis.

Bile acids (BAs), synthesized in the liver and modified by the gut microbiota, have been widely appreciated not only as simple lipid emulsifiers, but also as complex metabolic regulators and momentous signaling molecules, which play prominent roles in the complex interaction among several metabolic systems. Recent studies have drawn us eyes on the diverse physiological functions of BAs, to enlarge the knowledge about the "gut-bone" axis due to the participation about the gut microbiota-derived BAs to modulate bone homeostasis at physiological and pathological stations. In this review, we have summarized the metabolic processes of BAs and highlighted the crucial roles of BAs targeting bile acid-activated receptors, promoting the proliferation and differentiation of osteoblasts (OBs), inhibiting the activity of osteoclasts (OCs), as well as reducing articular cartilage degradation, thus facilitating bone repair.

Osteoclast-derived apoptotic bodies inhibit naive CD8 T cell activation via Siglec15, promoting breast cancer secondary metastasis.

The bone microenvironment promotes cancer cell proliferation and dissemination. During periodic bone remodeling, osteoclasts undergo apoptosis, producing large numbers of apoptotic bodies (ABs). However, the biological role of osteoclast-derived ABs, which are residents of the bone-tumor niche, remains largely unknown.

PTP1B knockdown alleviates BMSCs senescence via activating AMPK-mediated mitophagy and promotes osteogenesis in senile osteoporosis.

The senescence of bone marrow mesenchymal stem cells (BMSCs) is the basis of senile osteoporosis (SOP). Targeting BMSCs senescence is of paramount importance for developing anti-osteoporotic strategy. In this study, we found that protein tyrosine phosphatase 1B (PTP1B), an enzyme responsible for tyrosine dephosphorylation, was significantly upregulated in BMSCs and femurs with advancing chronological age.

Reduced osteoclast-derived apoptotic bodies in bone marrow characterizes the pathological progression of osteoporosis.

Osteoporosis is associated with excessive activity of osteoclasts. In bone turn over, most osteoclasts undergo apoptosis after bone resorption and produce a large number of apoptotic bodies (ABs). However, the biological function of osteoclast-derived apoptotic bodies (OC-ABs) in the progression of osteoporosis is still unknow.

Gold-nanosphere mitigates osteoporosis through regulating TMAO metabolism in a gut microbiota-dependent manner.

Osteoporosis (OP) is a metabolic bone disease characterized by decreased bone mass and increased bone fragility. The imbalance of bone homeostasis modulated by osteoclasts and osteoblasts is the most crucial pathological change in osteoporosis. As a novel treatment strategy, nanomedicine has been applied in drug delivery and targeted therapy due to its high efficiency, precision, and fewer side effects.

Ghost messages: cell death signals spread.

Cell death is a mystery in various forms. Whichever type of cell death, this is always accompanied by active or passive molecules release. The recent years marked the renaissance of the study of these molecules showing they can signal to and communicate with recipient cells and regulate physio- or pathological events.

Osteoclast-derived extracellular miR-106a-5p promotes osteogenic differentiation and facilitates bone defect healing.

Small extracellular vesicles (sEVs) are considered to play critical roles in intercellular communications during normal and pathological processes since they are enriched with miRNAs and other signal molecules. In bone remodeling, osteoclasts generate large amounts of sEVs. However, there is very few research studying whether and how osteoclast-derived sEVs (OC-sEVs) affect surrounding cells.

Endothelial Cells Promote Migration of Mesenchymal Stem Cells via PDGF-BB/PDGFR-Src-Akt in the Context of Inflammatory Microenvironment upon Bone Defect.

Homing of mesenchymal stem cells (MSCs) to the defect site is indispensable for bone repair. Local endothelial cells (ECs) can recruit MSCs; however, the mechanism remains unclear, especially in the context of the inflammatory microenvironment. This study was aimed to investigate the role of ECs in MSCs migration during the inflammatory phase of bone repair.

Sialylation of TLR2 initiates osteoclast fusion.

The molecular control of osteoclast formation is still not clearly elucidated. Here, we show that a process of cell recognition mediated by Siglec15-TLR2 binding is indispensable and occurs prior to cell fusion in RANKL-mediated osteoclastogenesis. Siglec15 has been shown to regulate osteoclastic bone resorption.

Modulation of SIRT6 activity acts as an emerging therapeutic implication for pathological disorders in the skeletal system.

The skeletal system is a dynamically balanced system, which undergoes continuous bone resorption and formation to maintain bone matrix homeostasis. As an important ADP-ribosylase and NAD-dependent deacylase, SIRT6 (SIR2-like protein 6) is widely expressed on various kinds of bone cells, such as chondrocytes, osteoblasts, osteoclasts. The aberration of SIRT6 impairs gene expression (e.

Klotho upregulates the interaction between RANK and TRAF6 to facilitate RANKL-induced osteoclastogenesis via the NF-κB signaling pathway.

Background: α-Klotho (Klotho) plays a wide range of roles in pathophysiological processes, such as low-turnover osteoporosis observed in klotho mutant mice (kl/kl mice). However, the precise function and underlying mechanism of klotho during osteoclastogenesis are not fully understood. Here, we investigated the effects of klotho on osteoclastogenesis induced by receptor activator of nuclear factor kappa-B ligand (RANKL).

Beyond immunosuppressive effects: dual roles of myeloid-derived suppressor cells in bone-related diseases.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells (IMCs) with immunosuppressive functions, whereas IMCs originally differentiate into granulocytes, macrophages, and dendritic cells (DCs) to participate in innate immunity under steady-state conditions. At present, difficulties remain in identifying MDSCs due to lacking of specific biomarkers. To make identification of MDSCs accurately, it also needs to be determined whether having immunosuppressive functions.

Bone-targeted pH-responsive cerium nanoparticles for anabolic therapy in osteoporosis.

Antiresorptive drugs are widely used for treatment of osteoporosis and cancer bone metastasis, which function mainly through an overall inhibition of osteoclast. However, not all osteoclasts are "bone eaters"; preosteoclasts (pOCs) play anabolic roles in bone formation and angiogenesis through coupling with osteoblasts and secreting platelet derived growth factor-BB (PDGF-BB). In this study, a bone-targeted pH-responsive nanomaterial was designed for selectively eliminating mature osteoclasts (mOCs) without affecting pOCs.

Light rare earth elements hinder bone development via inhibiting type H vessels formation in mice.

Light rare earth elements (LREEs) are widely used in medical, industrial, and agricultural fields. Wide application of light rare earth and exposure to these elements in human society leads to increasing accumulation of LREE in human skeletal system. However, the effects of LREEs on human bone health is not clear.

Osteoclast-derived small extracellular vesicles induce osteogenic differentiation via inhibiting ARHGAP1.

Activated osteoclasts release large amounts of small extracellular vesicles (sEVs) during bone remodeling. However, little is known about whether osteoclast-derived sEVs affect surrounding cells. In this study, osteoclasts were generated by stimulating bone marrow macrophages (BMMs) with macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear actor κB ligand (RANKL).

Small extracellular vesicles deliver osteolytic effectors and mediate cancer-induced osteolysis in bone metastatic niche.

Extracellular vesicles (EVs) play critical roles in regulating bone metastatic microenvironment through mediating intercellular crosstalks. However, little is known about the contribution of EVs derived from cancer cells to the vicious cycle of bone metastasis. Here, we report a direct regulatory mode between tumour cells and osteoclasts in metastatic niche of prostate cancer via vesicular miRNAs transfer.

Osteoclast-derived apoptotic bodies couple bone resorption and formation in bone remodeling.

Bone remodeling is precisely coordinated by bone resorption and formation. Apoptotic osteoclasts generate large amounts of apoptotic bodies (ABs) marking the end of the bone resorption phase, whereas the functions of osteoclast-derived ABs remain largely unknown. Here, we identified the molecular profile of ABs derived from osteoclasts at distinct differentiation stages and investigated their corresponding functions.

Microenvironment in subchondral bone: predominant regulator for the treatment of osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease in the elderly. Although OA has been considered as primarily a disease of the articular cartilage, the participation of subchondral bone in the pathogenesis of OA has attracted increasing attention. This review summarises the microstructural and histopathological changes in subchondral bone during OA progression that are due, at the cellular level, to changes in the interactions among osteocytes, osteoblasts, osteoclasts (OCs), endothelial cells and sensory neurons.

Long non-coding RNA HCAR promotes endochondral bone repair by upregulating VEGF and MMP13 in hypertrophic chondrocyte through sponging miR-15b-5p.

Endochondral bone formation is an important route for bone repair. Although emerging evidence has revealed the functions of long non-coding RNAs (lncRNAs) in bone and cartilage development, the effect of lncRNAs in endochondral bone repair is still largely unknown. Here, we identified a lncRNA, named Hypertrophic Chondrocyte Angiogenesis-related lncRNA (HCAR), and proved it to promote the endochondral bone repair by upregulating the expression of matrix metallopeptidase 13 (Mmp13) and vascular endothelial growth factor α (Vegfa) in hypertrophic chondrocytes.