Bone specific alkaline phosphatase

The balance between Noggin and bone morphogenetic proteins (BMPs) is important during early development and skeletal regenerative therapies. Noggin binds BMPs in the extracellular space, thereby preventing BMP signaling. However, Noggin may affect cell response not necessarily through the modulation of BMP signaling, raising the possibility of direct Noggin signaling through yet unspecified receptors. Here we show that in osteogenic cultures of adipose-derived stem cells (ASCs), Noggin activates fibroblast growth factor receptors (FGFRs), Src/Akt and ERK kinases, and it stabilizes TAZ proteins in the presence of dexamethasone...

Tissue-nonspecific alkaline phosphatase (TNALP) is a glycoprotein expressed by osteoblasts that promotes bone mineralization. TNALP catalyzes the hydrolysis of the mineralization inhibitor inorganic pyrophosphate and ATP to provide inorganic phosphate, thus controlling the inorganic pyrophosphate/inorganic phosphate ratio to enable the growth of hydroxyapatite crystals. N-linked glycosylation of TNALP is essential for protein stability and enzymatic activity and is responsible for the presence of different bone isoforms of TNALP associated with functional and clinical differences...

Bone defects show a slow rate of osteoconduction and imperfect reconstruction, and the current treatment strategies to treat bone defects suffer from limitations like immunogenicity, lack of cell adhesion, and the absence of osteogenic activity. In this context, bioactive supramolecular peptides and peptide gels offer unique opportunities to develop biomaterials that can play a dominant role in the biomineralization of bone tissues and promote bone formation. In this article, we have demonstrated the potential of six tetrapeptides for specific binding to hydroxyapatite (HAp), a major inorganic component of the bone, and their effect on the growth and osteogenic differentiation of mesenchymal stem cells (MSCs)...

Stem cell-derived extracellular vesicles (EVs) show great potential for promoting bone tissue regeneration. However, normal EVs (Nor-EVs) have a limited ability to direct tissue-specific regeneration. Therefore, it is necessary to optimize the osteogenic capacity of EV-based systems for repairing extensive bone defects. Herein, we show that hydrogels loaded with osteoinductive dental pulp stem cell-derived EVs (Ost-EVs) enhanced bone tissue remodeling, resulting in a 2.23 ± 0.25-fold increase in the expression of bone morphogenetic protein 2 (BMP2) compared to the hydrogel control group...

Macrophages are key regulators in bone repair and regeneration. Recent studies have shown that long-term epigenetic changes and metabolic shifts occur during specific immune training of macrophages that affect their functional state, resulting in heightened (trained) or reduced (tolerant) responses upon exposure to a second stimulus. This is known as innate immune memory. Here, we study the impact of macrophages' memory trait on osteoblast differentiation of human mesenchymal stromal cells (hMSCs) and osteoclast differentiation...

OBJECTIVE: This study aimed to determine the prognostic value of the flare phenomenon in patients with metastatic castration-resistant prostate cancer (mCRPC) using the bone scan index (BSI) derived from 99m Tc-methylenediphosphonate (MDP) bone scintigraphy images. METHODS: We categorized 72 patients from the PROSTAT-BSI registry with mCRPC who were followed-up for 2 years after starting docetaxel chemotherapy to groups based on pre-chemotherapy BSI values of < 1, 1-4, and > 4...

INTRODUCTION: This study aimed to synthesize existing evidence on the potential association between obstructive sleep apnea (OSA) and low bone mass in adults. METHODS: Electronic searches of four main databases were performed. The inclusion criteria consisted of observational studies investigating the relationship between OSA and bone mass, osteoporosis, fractures, or bone metabolism markers in adult population. Bone mineral density (BMD) and T score of lumbar and femur neck, incidence of osteoporosis and fractures, bone metabolism marker levels were extracted as primary outcomes...

Patients implanted with osseointegrated (OI) prosthetic systems have reported vastly improved upper and lower extremity prosthetic function compared with their previous experience with socket-suspension systems. However, OI systems have been associated with superficial and deep-bone infections and implant loosening due, in part, to a failure of the osseointegration process. Although monitoring the osseointegration using circulating biomarkers has clinical relevance for understanding the progression of osseointegration with these devices, it has yet to be established...

Three-dimensional (3D) printing allows precise manufacturing of bone scaffolds for patient-specific applications and is one of the most recently developed and implemented technologies. In this study, a bilayer and multimaterial alginate dialdehyde-gelatin (ADA-GEL) scaffolds incorporating polydopamine (PDA)/SiO2 -CaO nanoparticle complexes was 3D printed using a pneumatic extrusion-based 3D printing technology and further modified on the surface with bovine serum albumin (BSA) for application in critical-sized bone regeneration...

OBJECTIVES: Steroid-induced osteonecrosis of the femoral head (SONFH) is characterized by impaired osteogenesis in bone marrow mesenchymal stem cells (BMSCs). This study investigates the role of lysine-specific demethylase 5A (KDM5A) in SONFH to identify potential therapeutic targets. METHODS: Human BMSCs were isolated and characterized for cell surface markers and differentiation capacity. A SONFH cell model was established using dexamethasone treatment. BMSCs were transfected with KDM5A overexpression vectors or si-KDM5A, and the expression of KDM5A, miR-107, runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), and osteopontin (OPN) was assessed...

This work presents the effect of the silicocarnotite (SC) and nagelschmidtite (Nagel) phases on in vitro osteogenesis. The known hydroxyapatite of biological origin (BHAp) was used as a standard of osteoconductive characteristics. The evaluation was carried out in conventional and osteogenic media for comparative purposes to assess the osteogenic ability of the bioceramics. First, the effect of the material on cell viability at 24 h, 7 and 14 days of incubation was evaluated. In addition, cell morphology and attachment on dense bioceramic surfaces were observed by fluorescence microscopy...

Imaging before 223 Ra-dichloride (223 Ra) therapy is crucial for selecting metastatic castration-resistant prostate cancer (mCRPC) patients with bone-only disease. The purpose of this study was to evaluate if baseline prostate-specific membrane antigen (PSMA) PET/CT (bPSMA) versus CT is associated with outcomes of 223 Ra therapy. Methods: A secondary analysis of the data of a prospective observational study (NCT04995614) was performed. Patients received a maximum of 6 223 Ra cycles and were retrospectively divided into the bPSMA or baseline CT (bCT) groups...

The quest for finding a suitable scaffold system that supports cell survival and function and, ultimately, the regeneration of the pulp-dentin complex remains challenging. Herein, we hypothesized that dental pulp stem cells (DPSCs) encapsulated in a collagen-based hydrogel with varying stiffness would regenerate functional dental pulp and dentin when concentrically injected into the tooth slices. Collagen hydrogels with concentrations of 3 mg/mL (Col3) and 10 mg/mL (Col10) were prepared, and their stiffness and microstructure were assessed using a rheometer and scanning electron microscopy, respectively...

Biomimetic scaffolds provide the essential biophysical (e.g., surface topography, stiffness) and biochemical cues (e.g., composition) to guide cell morphology, proliferation, and differentiation. Although the effects of biomaterial-directed cues on cell response have been widely reported, few studies have sought to decouple these effects to better understand the interplay between the different physicochemical factors on tissue-specific cell function. Herein, beta-tricalcium phosphate (β-TCP) was incorporated into electrochemically aligned collagen (ELAC) and random collagen threads, and the individual and interactive effects of collagen alignment (i...

Patients with bone diseases often experience increased bone fragility. When bone injuries exceed the body's natural healing capacity, they become significant obstacles. The global rise in the aging population and the escalating obesity pandemic are anticipated to lead to a notable increase in acute bone injuries in the coming years. Our research developed a novel DLP resin for 3D printing, utilizing poly(ethylene glycol diacrylate) (PEGDA) and various monomers through the PET-RAFT polymerization method. To enhance the performance of bone scaffolds, triply periodic minimal surfaces (TPMS) were incorporated into the printed structure, promoting porosity and pore interconnectivity without reducing the mechanical resistance of the printed piece...

One of the key challenges in biofabrication applications is to obtain bioinks that provide a balance between printability, shape fidelity, cell viability, and tissue maturation. Decellularization methods allow the extraction of natural extracellular matrix (ECM), preserving tissue-specific matrix proteins. However, the critical challenge in bone decellularization is to preserve both organic (collagen, proteoglycans) and inorganic components (hydroxyapatite) to maintain the natural composition and functionality of bone...

During orthodontic tooth movement (OTM), areas of compressive and tensile forces are generated in the periodontal ligament (PdL), a mechanoreactive connective tissue between the teeth and alveolar bone. Mechanically stimulated PdL fibroblasts (PdLFs), the main cell type of PdL, express significantly increased levels of growth differentiation factor 15 (GDF15). In compressed PdL areas, GDF15 plays a fundamental role in modulating relevant OTM processes, including inflammation and osteoclast activation. However, the specific function of this factor in tensile areas has not yet been investigated...

BACKGROUND: Recently, serum sialic acid (SA) has emerged as a distinct prognostic marker for prostate cancer (PCa) and bone metastases, warranting differential treatment and prognosis for low-volume (LVD) and high-volume disease (HVD). In clinical settings, evaluating bone metastases can prove advantageous. OBJECTIVES: We aimed to establish the correlation between SA and both bone metastasis and HVD in newly diagnosed PCa patients. METHODS: We conducted a retrospective analysis of 1202 patients who received a new diagnosis of PCa between November 2014 and February 2021...

Hypophosphatasia (HPP), also called Rathbun disease, is a rare genetic disorder that is caused by the loss-of-function mutation in the ALPL gene encoding tissue non-specific alkaline phosphatase. Doctor Rathbun first described the case of a 3-week-old infant who presented with severe osteopenia, rickets, and multiple radiographic fractures, and died shortly after of epileptic seizure and respiratory distress. The term "hypophosphatasia" was coined as the patients' alkaline phosphatase levels were significantly low...

OBJECTIVE: This study aims to analyse factors influencing bone metastasis in prostate cancer and the diagnostic value of serum prostate-specific antigen (PSA), and D-dimer (D-D) combined with cystatin C (CysC) in bone metastasis of prostate cancer. METHODS: Data of 116 patients with prostate cancer admitted to our hospital were retrospectively analysed. They were divided into two groups: Bone metastasis group (46 cases) and non-bone metastasis group (70 cases). Univariate and multivariate logistic regression analyses were used to determine factors influencing bone metastasis in prostate cancer...