Phosphate Metabolism and Pathophysiology in Parathyroid Disorders and Endocrine Tumors

The advent of new insights into phosphate metabolism must urge the endocrinologist to rethink the pathophysiology of widespread disorders, such as primary hyperparathyroidism, and also of rarer endocrine metabolic bone diseases, such as hypoparathyroidism and tumor-induced hypophosphatemia. These rare diseases of mineral metabolism have been and will be a precious source of new information about phosphate and other minerals in the coming years. The parathyroid glands, the kidneys, and the intestine are the main organs affecting phosphate levels in the blood and urine. Parathyroid disorders, renal tubule defects, or phosphatonin-producing tumors might be unveiled from alterations of such a simple and inexpensive mineral as serum phosphate. This review will present all these disorders from a ‘phosphate perspective’.

METTL3-Dependent Glycolysis Regulates Dental Pulp Stem Cell Differentiation

N6-methyladenosine (m6A) is a eukaryotic messenger RNA modification catalyzed by methyltransferase-like 3 (METTL3), which is involved in various developmental and disease processes. However, the connection between the epigenetic modification of m6A and glucose metabolism during osteogenesis is still unclear. Here, we show that interference with METTL3 in dental pulp stem cells (DPSCs) inhibits cell proliferation and osteogenic differentiation. Moreover, transcriptome sequencing and metabolic testing were used to explore the mechanism between glucose metabolism and m6A modification in METTL3-knockdown DPSCs. Methylated RNA immunoprecipitation–quantitative polymerase chain reaction and RNA stability assays were used to determine the target genes of METTL3. Mechanistically, METTL3 directly interacts with ATP citrate lyase (ACLY) and a mitochondrial citrate transporter (SLC25A1) and then further affects the glycolytic pathway. M6A-mediated ACLY and SLC25A1 stability depends on the m6A readers IGF2BP2 and IGF2BP2/3, respectively. Our experiments uncovered the potential molecular mechanism of epigenetic modification in osteogenic differentiation, providing new ideas for the clinical application of stem cells and the intervention of metabolic bone diseases.

PHYSIOLOGICAL ASPECTS OF ASTHIDHATU

Ayurveda is an ancient medical science which is related to health. Ayurveda described three basic physiological constitution of the body they are: Dosha, Dhatu and mala. Dhatu are structural unit of the body. Asthi is fifth dhatu among saptadhatu. In modern science asthidhatu relate with bones and cartilage. Bones store minerals such as calcium. Metabolic bone diseases are caused by minerals and vitamins deficiency. Asthidhatu is resultant of action of medoagni on medodhatu and is responsible for nourishing majjadhatu. It supports the basic structures, protect vital organs, nourishing the nervous tissue. Health refers to the moderate quantity of asthidhatu while dis- orders may develop when any vitiation occur. Just as asthi dhatu (Bones) contribute to health, diseases related to bones can disrupt the body. This paper attempts to understand concepts of Asthidhatu for maintain health and pre- vention from diseases related to the bone. Keywords: Health, Asthidhatu ksaya-Vruddhi, functions

H2S Donor and Bone Metabolism

Hydrogen sulfide (H2S) has been recognized as the third gasotransmitter, following nitric oxide and carbon monoxide, and it exerts important biological effects in the body. Growing evidence has shown that H2S is involved in many physiological processes in the body. In recent years, much research has been carried out on the role of H2S in bone metabolism. Bone metabolic diseases have been linked to abnormal endogenous H2S functions and metabolism. It has been found that H2S plays an important role in the regulation of bone diseases such as osteoporosis and osteoarthritis. Regulation of H2S on bone metabolism has many interacting signaling pathways at the molecular level, which play an important role in bone formation and absorption. H2S releasing agents (donors) have achieved significant effects in the treatment of metabolic bone diseases such as osteoporosis and osteoarthritis. In addition, H2S donors and related drugs have been widely used as research tools in basic biomedical research and may be explored as potential therapeutic agents in the future. Donors are used to study the mechanism and function of H2S as they release H2S through different mechanisms. Although H2S releasers have biological activity, their function can be inconsistent. Additionally, donors have different H2S release capabilities, which could lead to different effects. Side effects may form with the formation of H2S; however, it is unclear whether these side effects affect the biological effects of H2S. Therefore, it is necessary to study H2S donors in detail. In this review, we summarize the current information about H2S donors related to bone metabolism diseases and discuss some mechanisms and biological applications.

Current Approaches in Chronic Pancreatitis

Chronic pancreatitis is a fibroinflammatory syndrome of the pancreas that results in exocrine and endocrine pancreatic insufficiency and chronic pain. It can be seen in all age groups depending on the etiologic factors. It is believed that alcohol is one of the major etiologic factors of chronic pancreatitis, but it is now recognized that alcohol is responsible for 50% of the cases. Mutations in many genes such as PRSS1, SPINK1, CTRC, CFTR are identified as causative or predisposing factors for CP. Early diagnosis and staging of CP are still a challenge in clinic. Although the chief complaint of patients with CP is abdominal pain, CP can cause many disorders such as diabetes or metabolic bone diseases. The treatment of CP mainly depends on the severity of the disease and morphology of the pancreas. Medical therapy, endoscopy and surgery are all used for the treatment of CP and its complications.

Fractures in Corticosteroid- and Bisphosphonate-treated Subjects With Longstanding Rheumatoid Arthritis

Background: Bisphosphonates are the most widely prescribed agents for the treatment of postmenopausal osteoporosis and other metabolic bone diseases. Atypical femoral fractures in bisphosphonate-treated patients have raised concerns regarding the long-term safety of this class of medications. Case Presentation: In this study, we report two patients suffering from fractures while receiving biphosphonates; a postmenopausal patient with rheumatoid arthritis and a history of long-term use of bisphosphonates and glucocorticoids presenting with multiple fractures as case one and another 52-year-old female patient diagnosed with Systemic Lupus Erythematosus (SLE) who suffered from a femoral shaft fracture without any history of prior traumatic incidents as case two. Conclusions: Considering the low risk for atypical femoral fractures, further careful screening for these types of fractures should be undertaken. In addition, in order to lower the rate of fractures in patients on long-term bisphosphonate therapy, assessment of patients’ contralateral side should be considered to prevent further fractures, especially in patients with prodromal pain.

Analysis of Bone Microarchitectural Changes and Structural Damage in Sickle Cell Disease-Induced Avascular Necrosis Using Raman Spectroscopy

Objectives: Bone failure due to avascular necrosis (AVN) is a complex pathological phenomenon. Analysis of molecular changes in the bone matrix may help to shed light on the disease process and guide management. This study aimed to explore changes in bone quality and structural damage caused by sickle cell disease (SCD)- induced AVN using Raman spectroscopy. Methods: A total of 10 necrotic femoral heads were obtained from seven SCD patients who underwent total hip replacements. The femoral heads were cut in half and scanned using Raman spectroscopy in correlation with preoperative magnetic resonance imaging to identify necrotic and healthy control areas. Subsequently, samples were examined to determine changes in bone mineralisation, crystallinity, carbonate content, collagen cross-linking and mineral and collagen fibril orientation. Results: Significant changes were observed in bone mineral content, mineral-to-organic content and collagen fibril orientation in necrotic compared to control areas (P ≤0.050). Conclusion: The necrotic samples displayed severe structural damage and loss of mineral and organic contents. Similar Raman signals have been reported in other metabolic bone diseases such as osteoporosis, thereby potentially supporting the use of medical treatment in AVN to promote bone quality. Keywords: Sickle Cell Disease; Osteonecrosis; Femur Head Necrosis; Bone Mineralization; Bone Density; Bone Remodeling; Extracellular Matrix; Raman Spectroscopy.