Nicotinamide (NAM), a water-soluble derivative of vitamin B3, has emerged as a potential therapeutic agent for bone-related disorders. In particular, it promotes bone metabolism and alleviates delayed tooth eruptions associated with cleidocranial dysplasia (CCD). NAM serves as a precursor for nicotinamide adenine dinucleotide, a key coenzyme involved in cellular metabolism that plays an essential role in oxidative phosphorylation and mitochondrial function. Recent research has highlighted the capacity of NAM to enhance osteogenic differentiation and regulate the interaction between osteoblasts and osteoclasts, which is critical for maintaining bone homeostasis. Moreover, the effect of NAM in preventing delayed tooth eruptions in CCD models underscores its potential as a noninvasive therapeutic option. Considering its safety profile and therapeutic potential, NAM is a promising candidate for long-term treatment of bone diseases and prevention of age-related bone disorders.

Coronavirus disease 2019 (COVID-19) is a highly contagious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This disease is characterized by a wide spectrum of symptoms, ranging from mild to severe, including fatal outcomes. This study aims to review gustatory and salivary secretion dysfunctions and determine their potential pathogenic mechanisms. Gustatory impairment and salivary dysfunction are prevalent among patients with acute COVID-19 and those recovering from the disease. The mouth serves as a critical entry route for SARS-CoV-2. The cells within the oral epithelium, taste buds, and minor and major salivary glands express key entry factors for SARS-CoV-2, including angiotensin-converting enzyme 2, transmembrane serine protease 2, and furin. The co-occurrence of gustatory and salivary secretion dysfunctions possibly has pathogenetic association with the following factors: the expression of SARS-CoV-2 cellular entry receptors in the taste buds and salivary glands and SARS-CoV-2-induced zinc deficiency, which is crucial for normal taste perception and saliva secretion. Furthermore, the cytokine storm triggered by COVID-19 contributes to secondary damage affecting gustatory and salivary functions.

Sestrin 2 (SESN2) is a member of the sestrin family of stress-induced proteins that negatively regulate aging-associated biological processes. This study aims to investigate the role of SESN2 in regulating the differentiation potential and senescence of mesenchymal stem cells (MSCs) derived from young and elderly donors. Bulk RNA sequencing revealed a common decline in the SESN2 mRNA levels in MSCs from elderly individuals, which was confirmed via reverse transcription-polymerase chain reaction and western blot analyses. SESN2 knockdown in MSCs from young donors resulted in phenotypic changes similar to those in MSCs from elderly donors, including an enhanced expression of senescence and adipogenic markers and diminished expression of osteogenic markers. To confirm the effect of decreased SESN2 expression on osteogenic and adipogenic differentiation, we induced Sesn2 knockdown in mouse bone marrow-derived MSCs. Sesn2 knockdown suppressed the mRNA expression of osteogenic marker genes, alkaline phosphatase activity, and matrix mineralization. Furthermore, Sesn2 knockdown enhanced mRNA expression of the adipogenic marker genes and intracellular lipid accumulation. These results suggest that a decline in SESN2 expression during aging contributes to the shift of MSC differentiation from osteogenic to adipogenic lineage.

Periodontal disease (PD) is strongly linked to increased risk of oral squamous cell carcinoma (OSCC); however, the specific mechanism through which the development of PD and OSCC is simultaneously promoted remains unclear. This study explored the impact of periodontal pathogens on OSCC progression and the contribution of periodontal pathogen-stimulated OSCC to PD development. The expression of osteoclastogenesis-inducing factors was assessed using quantitative reverse transcription polymerase chain reaction analysis following stimulation of OSCC with lipopolysaccharide (LPS) derived from the periodontal pathogen Porphyromonas gingivalis (Pg), a pathogen commonly responsible for PD. The cell counting kit-8 assay was used to determine the effects of Pg-LPS on OSCC proliferation and drug resistance to cisplatin and 5-fluorouracil. The effects of conditioned medium (CM) derived from Pg-LPS-stimulated OSCC on osteoclastogenesis was evaluated using tartrate-resistant acid phosphatase (TRAP) staining on bone marrow-derived macrophages (BMMs). Pg-LPS administration in SCC-25 and YD-8 OSCC cell lines induced a significant increase in receptor activator of nuclear factor kappa-B ligand mRNA expression; however, it did not affect cell proliferation. Treatment with CM derived from Pg-LPS-stimulated SCC-25 or YD-8 cells markedly enhanced the formation of TRAP-positive multinucleated cells during osteoclast differentiation of BMMs. Altogether, these findings demonstrate that Pg-LPS-stimulated OSCC promoted osteoclastogenesis through a paracrine mechanism.