The role of autophagy/lipophagy in the response of osteoblastic cells to hyperlipidemia (Review).

There has been interest in the connection between cardiovascular diseases and osteoporosis, both of which share hyperlipidemia as a common pathological basis. Osteoporosis is a progressive metabolic bone disease characterized by reduced bone mass, deteriorated bone microstructure, increased bone fragility and heightened risk of bone fractures. Dysfunction of osteoblastic cells, vital for bone formation, is induced by excessive internalization of lipids under hyperlipidemic conditions, forming the crux of hyperlipidemia-associated osteoporosis.

VAMP2 controls murine epidermal differentiation and carcinogenesis by regulation of nucleophagy.

Differentiation of murine epidermal stem/progenitor cells involves the permanent withdrawal from the cell cycle, the synthesis of various protein and lipid components for the cornified envelope, and the controlled dissolution of cellular organelles and nuclei. Deregulated epidermal differentiation contributes to the development of various skin diseases, including skin cancers. With a genome-wide shRNA screen, we identified vesicle-associated membrane protein 2 (VAMP2) as a critical factor involved in skin differentiation.

BMP and activin receptor membrane bound inhibitor: BAMBI has multiple roles in gene expression and diseases (Review).

BMP and activin membrane-bound inhibitor (BAMBI) is a transmembrane glycoprotein, known as a pseudo-receptor for TGFβ, as, while its extracellular domain is similar to that of type I TGFβ receptors, its intracellular structure is shorter and lacks a serine/threonine phosphokinase signaling motif. BAMBI can regulate numerous biological phenomena, including glucose and lipid metabolism, inflammatory responses, and cell proliferation and differentiation. Furthermore, abnormal expression of BAMBI at the mRNA and protein levels contributes to various human pathologies, including obesity and cancer.

MACF1 promotes osteoblastic cell migration by regulating MAP1B through the GSK3beta/TCF7 pathway.

Rationale: The migration of osteoblastic cells to bone formation surface is an essential step for bone development and growth. However, whether the migration capacity of osteoblastic cells is compromised during osteoporosis occurrence and how it contributes to bone formation reduction remain unexplored so far. In this work, we found, as a positive regulator of cell migration, microtubule actin crosslinking factor 1 (MACF1) enhanced osteoblastic cells migration.

miR-129-5p Inhibits Bone Formation Through TCF4.

Osteoporosis is a frequently occurring bone disease in middle-aged and aged men and women. However, current therapies on this disease are still not ideal. MicroRNAs (miRNAs) are a class of endogenous non-protein-coding RNA with a length of 18-25 nucleotides.

Silencing of miR-138-5p sensitizes bone anabolic action to mechanical stimuli.

Emerging evidence is revealing that microRNAs (miRNAs) play essential roles in mechanosensing for regulating osteogenesis. However, no mechanoresponsive miRNAs have been identified in human bone specimens. Bedridden and aged patients, hindlimb unloaded and aged mice, and Random Positioning Machine and primary aged osteoblasts were adopted to simulate mechanical unloading conditions at the human, animal and cellular levels, respectively.

Long noncoding RNA AK039312 and AK079370 inhibits bone formation via miR-199b-5p.

Osteoporosis caused by aging and menopause had become an emerging threat to human health. The reduction of osteoblast differentiation has been considered to be an essential cause of osteoporosis. Osteoblast differentiation could be regulated by LncRNAs, and increasing evidences have proved that LncRNAs may be adopted as potential therapeutic targets for osteoporosis.

Bone Microenvironment and Osteosarcoma Metastasis.

The bone microenvironment is an ideal fertile soil for both primary and secondary tumors to seed. The occurrence and development of osteosarcoma, as a primary bone tumor, is closely related to the bone microenvironment. Especially, the metastasis of osteosarcoma is the remaining challenge of therapy and poor prognosis.

Mesenchymal MACF1 Facilitates SMAD7 Nuclear Translocation to Drive Bone Formation.

Microtubule actin crosslinking factor 1 (MACF1) is a large crosslinker that contributes to cell integrity and cell differentiation. Recent studies show that MACF1 is involved in multiple cellular functions such as neuron development and epidermal migration, and is the molecular basis for many degenerative diseases. MACF1 is highly abundant in bones, especially in mesenchymal stem cells; however, its regulatory role is still less understood in bone formation and degenerative bone diseases.

MACF1 promotes preosteoblast migration by mediating focal adhesion turnover through EB1.

Microtubule actin crosslinking factor 1 (MACF1) is a widely expressed cytoskeletal linker and plays an essential role in various cells' functions by mediating cytoskeleton organization and dynamics. However, the role of MACF1 on preosteoblast migration is not clear. Here, by using MACF1 knockdown and overexpressed MC3T3-E1 cells, we found MACF1 positively regulated preosteoblast migration induced by cell polarization.

The Roles of FoxO Transcription Factors in Regulation of Bone Cells Function.

Forkhead box class O family member proteins (FoxOs) are evolutionarily conserved transcription factors for their highly conserved DNA-binding domain. In mammalian species, all the four FoxO members, FoxO1, FoxO3, FoxO4, and FoxO6, are expressed in different organs. In bone, the first three members are extensively expressed and more studied.

Silencing of lncRNA Promotes Osteoblast Differentiation and Bone Formation via β-Catenin/TCF1/Runx2 Signaling Axis.

Osteoporosis, a disease characterized by both loss of bone mass and structural deterioration of bone, is the most common reason for a broken bone among the elderly. It is known that the attenuated differentiation ability of osteogenic cells has been regarded as one of the greatest contributors to age-related bone formation reduction. However, the effects of current therapies are still unsatisfactory.

Mesenchymal Stem Cell Migration during Bone Formation and Bone Diseases Therapy.

During bone modeling, remodeling, and bone fracture repair, mesenchymal stem cells (MSCs) differentiate into chondrocyte or osteoblast to comply bone formation and regeneration. As multipotent stem cells, MSCs were used to treat bone diseases during the past several decades. However, most of these implications just focused on promoting MSC differentiation.

MiR-21-5p, miR-34a, and human telomerase RNA component as surrogate markers for cervical cancer progression.

Objective: This study aimed to demonstrate the predictive value of miR-21-5p, miR-34a, and human telomerase RNA component (hTERC) in cervical cancer (CC) development and evaluated their potential possibility for future clinical applications.

Methods: Specimens were collected from the normal cervix, cervical intraepithelial neoplasia (CIN) I, CIN II/III, cervical squamous cell carcinoma. Cytological evaluations and histopathologic examinations were conducted in all subjects, along with the assessment of human papillomavirus (HPV) DNA.

MACF1 Overexpression by Transfecting the 21 kbp Large Plasmid PEGFP-C1A-ACF7 Promotes Osteoblast Differentiation and Bone Formation.

Microtubule actin crosslinking factor 1 (MACF1) is a large spectraplakin protein known to have crucial roles in regulating cytoskeletal dynamics, cell migration, growth, and differentiation. However, its role and action mechanism in bone remain unclear. The present study investigated optimal conditions for effective transfection of the large plasmid PEGFP-C1A-ACF7 (∼21 kbp) containing full-length human MACF1 cDNA, as well as the potential role of MACF1 in bone formation.

Mechanical unloading reduces microtubule actin crosslinking factor 1 expression to inhibit β-catenin signaling and osteoblast proliferation.

Mechanical unloading was considered a major threat to bone homeostasis, and has been shown to decrease osteoblast proliferation although the underlying mechanism is unclear. Microtubule actin crosslinking factor 1 (MACF1) is a cytoskeletal protein that regulates cellular processes and Wnt/β-catenin pathway, an essential signaling pathway for osteoblasts. However, the relationship between MACF1 expression and mechanical unloading, and the function and the associated mechanisms of MACF1 in regulating osteoblast proliferation are unclear.

The Impact of Oxidative Stress on the Bone System in Response to the Space Special Environment.

The space special environment mainly includes microgravity, radiation, vacuum and extreme temperature, which seriously threatens an astronaut's health. Bone loss is one of the most significant alterations in mammalians after long-duration habitation in space. In this review, we summarize the crucial roles of major factors-namely radiation and microgravity-in space in oxidative stress generation in living organisms, and the inhibitory effect of oxidative stress on bone formation.

Microtubule actin crosslinking factor 1 promotes osteoblast differentiation by promoting β-catenin/TCF1/Runx2 signaling axis.

Osteoblast differentiation is a multistep process delicately regulated by many factors, including cytoskeletal dynamics and signaling pathways. Microtubule actin crosslinking factor 1 (MACF1), a key cytoskeletal linker, has been shown to play key roles in signal transduction and in diverse cellular processes; however, its role in regulating osteoblast differentiation is still needed to be elucidated. To further uncover the functions and mechanisms of action of MACF1 in osteoblast differentiation, we examined effects of MACF1 knockdown (MACF1-KD) in MC3T3-E1 osteoblastic cells on their osteoblast differentiation and associated molecular mechanisms.

MACF1, versatility in tissue-specific function and in human disease.

Spectraplakins are a family of evolutionarily conserved gigantic proteins and play critical roles in many cytoskeleton-related processes. Microtubule actin crosslinking factor 1 (MACF1) is one of the most versatile spectraplakin with multiple isoforms. As a broadly expressed mammalian spectraplakin, MACF1 is important in maintaining normal functions of many tissues.

Isoforms, structures, and functions of versatile spectraplakin MACF1.

Spectraplakins are crucially important communicators, linking cytoskeletal components to each other and cellular junctions. Microtubule actin crosslinking factor 1 (MACF1), also known as actin crosslinking family 7 (ACF7), is a member of the spectraplakin family. It is expressed in numerous tissues and cells as one extensively studied spectraplakin.

Knockdown of microtubule actin crosslinking factor 1 inhibits cell proliferation in MC3T3-E1 osteoblastic cells.

Microtubule actin crosslinking factor 1 (MACF1), a widely expressed cytoskeletal linker, plays important roles in various cells by regulating cytoskeleton dynamics. However, its role in osteoblastic cells is not well understood. Based on our previous findings that the association of MACF1 with F-actin and microtubules in osteoblast-like cells was altered under magnetic force conditions, here, by adopting a stable MACF1-knockdown MC3T3-E1 osteoblastic cell line, we found that MACF1 knockdown induced large cells with a binuclear/multinuclear structure.