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International Journal of Molecular... Oct 2023Osteoporosis is a widespread systemic disease characterized by a decrease in bone mass and an imbalance of the microarchitecture of bone tissue. Experimental and... (Review)
Review
Osteoporosis is a widespread systemic disease characterized by a decrease in bone mass and an imbalance of the microarchitecture of bone tissue. Experimental and clinical studies devoted to investigating the main pathogenetic mechanisms of osteoporosis revealed the important role of estrogen deficiency, inflammation, oxidative stress, cellular senescence, and epigenetic factors in the development of bone resorption due to osteoclastogenesis, and decreased mineralization of bone tissue and bone formation due to reduced function of osteoblasts caused by apoptosis and age-depended differentiation of osteoblast precursors into adipocytes. The current review was conducted to describe the basic mechanisms of the development of osteoporosis at molecular and cellular levels and to elucidate the most promising therapeutic strategies of pathogenetic therapy of osteoporosis based on articles cited in PubMed up to September 2023.
Topics: Humans; Osteogenesis; Osteoblasts; Osteoporosis; Bone and Bones; Osteoclasts; Cell Differentiation
PubMed: 37958752
DOI: 10.3390/ijms242115772 -
Periodontology 2000 Oct 2023The morphology and dimensions of the postextraction alveolar ridge are important for the surgical and restorative phases of implant treatment. Adequate new bone... (Review)
Review
The morphology and dimensions of the postextraction alveolar ridge are important for the surgical and restorative phases of implant treatment. Adequate new bone formation and preservation of alveolar ridge dimensions following extraction will facilitate installation of the implant in a restorative position, while preservation of soft tissue contour and volume is essential for an aesthetic and implant-supported restoration with healthy peri-implant tissues. Alveolar ridge preservation (ARP) refers to any procedure that aims to: (i) limit dimensional changes in the alveolar ridge after extraction facilitating implant placement without additional extensive bone and soft tissue augmentation procedures (ii) promote new bone formation in the healing alveolus, and (iii) promote soft tissue healing at the entrance of the alveolus and preserve the alveolar ridge contour. Although ARP is a clinically validated and safe approach, in certain clinical scenarios, the additional clinical benefit of ARP over unassisted socket healing has been debated and it appears that for some clinicians may represent an overtreatment. The aim of this critical review was to discuss the evidence pertaining to the four key objectives of ARP and to determine where ARP can lead to favorable outcomes when compared to unassisted socket healing.
Topics: Humans; Alveolar Ridge Augmentation; Tooth Extraction; Alveolar Process; Tooth Socket; Overtreatment; Alveolar Bone Loss
PubMed: 37622682
DOI: 10.1111/prd.12508 -
Aging Cell Jun 2023As we age, our bones undergo a process of loss, often accompanied by muscle weakness and reduced physical activity. This is exacerbated by decreased responsiveness to...
As we age, our bones undergo a process of loss, often accompanied by muscle weakness and reduced physical activity. This is exacerbated by decreased responsiveness to mechanical stimulation in aged skeleton, leading to the hypothesis that decreased mechanical stimulation plays an important role in age-related bone loss. Piezo1, a mechanosensitive ion channel, is critical for bone homeostasis and mechanotransduction. Here, we observed a decrease in Piezo1 expression with age in both murine and human cortical bone. Furthermore, loss of Piezo1 in osteoblasts and osteocytes resulted in an increase in age-associated cortical bone loss compared to control mice. The loss of cortical bone was due to an expansion of the endosteal perimeter resulting from increased endocortical resorption. In addition, expression of Tnfrsf11b, encoding anti-osteoclastogenic protein OPG, decreases with Piezo1 in vitro and in vivo in bone cells, suggesting that Piezo1 suppresses osteoclast formation by promoting Tnfrsf11b expression. Our results highlight the importance of Piezo1-mediated mechanical signaling in protecting against age-associated cortical bone loss by inhibiting bone resorption in mice.
Topics: Aged; Animals; Humans; Mice; Bone and Bones; Bone Diseases, Metabolic; Cortical Bone; Ion Channels; Mechanotransduction, Cellular; Osteoblasts; Osteoclasts
PubMed: 37147884
DOI: 10.1111/acel.13846 -
Periodontology 2000 Jun 2023Regenerative periodontal surgical procedures are an important component in the treatment of advanced periodontitis. They aim to improve the long-term prognosis of teeth... (Review)
Review
Regenerative periodontal surgical procedures are an important component in the treatment of advanced periodontitis. They aim to improve the long-term prognosis of teeth that are periodontally compromised by the presence of intrabony and/or furcation defects, resulting biologically in formation of root cementum, periodontal ligament, and alveolar bone and evidenced clinically by reduction of deep pockets to maintainable probing depths and/or improvements of vertical and horizontal furcation depth. Over the last 25 years, substantial clinical evidence has been accumulated to support the value of regenerative procedures in periodontally compromised dentitions. However, treatment success requires close attention to certain factors on the level of the patient, the tooth/defect, and the operator. Ignoring these factors in case selection, treatment planning, and treatment execution will increase the risk of complications that may jeopardize clinical success and may even be considered as treatment errors. Based on the currently available evidence from clinical practice guidelines, treatment algorithms, and on expert opinion, the present article provides an overview on the main factors, which influence the outcomes of regenerative periodontal surgery and gives recommendations on how to prevent complications and treatment errors.
Topics: Humans; Guided Tissue Regeneration, Periodontal; Oral Surgical Procedures; Treatment Outcome; Periodontitis; Prognosis; Alveolar Bone Loss; Furcation Defects
PubMed: 37435999
DOI: 10.1111/prd.12504 -
Annals of the Rheumatic Diseases Jan 2024To investigate the effect of the L-arginine metabolism on arthritis and inflammation-mediated bone loss.
OBJECTIVES
To investigate the effect of the L-arginine metabolism on arthritis and inflammation-mediated bone loss.
METHODS
L-arginine was applied to three arthritis models (collagen-induced arthritis, serum-induced arthritis and human TNF transgenic mice). Inflammation was assessed clinically and histologically, while bone changes were quantified by μCT and histomorphometry. In vitro, effects of L-arginine on osteoclast differentiation were analysed by RNA-seq and mass spectrometry (MS). Seahorse, Single Cell ENergetIc metabolism by profilIng Translation inHibition and transmission electron microscopy were used for detecting metabolic changes in osteoclasts. Moreover, arginine-associated metabolites were measured in the serum of rheumatoid arthritis (RA) and pre-RA patients.
RESULTS
L-arginine inhibited arthritis and bone loss in all three models and directly blocked TNFα-induced murine and human osteoclastogenesis. RNA-seq and MS analyses indicated that L-arginine switched glycolysis to oxidative phosphorylation in inflammatory osteoclasts leading to increased ATP production, purine metabolism and elevated inosine and hypoxanthine levels. Adenosine deaminase inhibitors blocking inosine and hypoxanthine production abolished the inhibition of L-arginine on osteoclastogenesis in vitro and in vivo. Altered arginine levels were also found in RA and pre-RA patients.
CONCLUSION
Our study demonstrated that L-arginine ameliorates arthritis and bone erosion through metabolic reprogramming and perturbation of purine metabolism in osteoclasts.
Topics: Humans; Mice; Animals; Osteoclasts; Arthritis, Rheumatoid; Arthritis, Experimental; Inflammation; Mice, Transgenic; Arginine; Inosine; Hypoxanthines; Purines; Bone Resorption
PubMed: 37775153
DOI: 10.1136/ard-2022-223626 -
Advanced Science (Weinheim,... Jun 2023Bone undergoes constant remodeling by osteoclast bone resorption coupled with osteoblast bone formation at the bone surface. A third major cell type in the bone is...
Bone undergoes constant remodeling by osteoclast bone resorption coupled with osteoblast bone formation at the bone surface. A third major cell type in the bone is osteocytes, which are embedded in the matrix, are well-connected to the lacunar network, and are believed to act as mechanical sensors. Here, it is reported that sympathetic innervation directly regulates lacunar osteocyte-mediated bone resorption inside cortical bone. It is found that sympathetic activity is elevated in different mouse models of bone loss, including lactation, ovariectomy, and glucocorticoid treatment. Further, during lactation elevated sympathetic outflow induces netrin-1 expression by osteocytes to further promote sympathetic nerve sprouting in the cortical bone endosteum in a feed-forward loop. Depletion of tyrosine hydroxylase-positive (TH ) sympathetic nerves ameliorated osteocyte-mediated perilacunar bone resorption in lactating mice. Moreover, norepinephrine activates β-adrenergic receptor 2 (Adrb2) signaling to promote secretion of extracellular vesicles (EVs) containing bone-degrading enzymes for perilacunar bone resorption and inhibit osteoblast differentiation. Importantly, osteocyte-specific deletion of Adrb2 or treatment with a β-blocker results in lower bone resorption in lactating mice. Together, these findings show that the sympathetic nervous system promotes osteocyte-driven bone loss during lactation, likely as an adaptive response to the increased energy and mineral demands of the nursing mother.
Topics: Female; Animals; Mice; Osteocytes; Lactation; Bone and Bones; Cortical Bone; Bone Resorption; Bone Diseases, Metabolic
PubMed: 37186379
DOI: 10.1002/advs.202207602 -
Nature Communications Oct 2023Although the gut microbiota has been reported to influence osteoporosis risk, the individual species involved, and underlying mechanisms, remain largely unknown. We...
Although the gut microbiota has been reported to influence osteoporosis risk, the individual species involved, and underlying mechanisms, remain largely unknown. We performed integrative analyses in a Chinese cohort of peri-/post-menopausal women with metagenomics/targeted metabolomics/whole-genome sequencing to identify novel microbiome-related biomarkers for bone health. Bacteroides vulgatus was found to be negatively associated with bone mineral density (BMD), which was validated in US white people. Serum valeric acid (VA), a microbiota derived metabolite, was positively associated with BMD and causally downregulated by B. vulgatus. Ovariectomized mice fed B. vulgatus demonstrated increased bone resorption and poorer bone micro-structure, while those fed VA demonstrated reduced bone resorption and better bone micro-structure. VA suppressed RELA protein production (pro-inflammatory), and enhanced IL10 mRNA expression (anti-inflammatory), leading to suppressed maturation of osteoclast-like cells and enhanced maturation of osteoblasts in vitro. The findings suggest that B. vulgatus and VA may represent promising targets for osteoporosis prevention/treatment.
Topics: Humans; Female; Mice; Animals; Gastrointestinal Microbiome; Bone Resorption; Osteoporosis
PubMed: 37891329
DOI: 10.1038/s41467-023-42005-y