Browsing by Subject "Bone loss"

Now showing 1 - 6 of 6
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    Acute Bone Loss and Infrapatellar Fat Pad Fibrosis in the Knee After an In Vivo ACL Injury in Adolescent Mice
    (Sage, 2023) Ahn, Taeyong; Loflin, Benjamin E.; Nguyen, Nicholas B.; Miller, Ciena K.; Colglazier, Kaitlyn A.; Wojtys, Edward M.; Schlecht, Stephen H.; Orthopaedic Surgery, School of Medicine
    Background: Young patients are 6 times more likely than adults to have a primary anterior cruciate ligament (ACL) graft failure. Biological factors (ie, tunnel osteolysis) may account for up to a third of these failures. Previous evaluations of patient ACL explants indicated significant bone loss within the entheseal regions. However, it remains unknown if the degree of bone loss within the ACL insertion regions, wherein ACL grafts are fixated, exceeds that of the femoral and tibial condylar bone. Hypothesis: Bone loss in the mineralized matrices of the femoral and tibial ACL entheses is distinct from that clinically reported across the whole knee after injury. Study design: Controlled laboratory study. Methods: We developed a clinically relevant in vivo mouse ACL injury model to cross-sectionally track the morphological and physiological postinjury changes within the ACL, femoral and tibial entheses, synovial joint space, and load-bearing epiphyseal cortical and trabecular bone components of the knee joint. Right ACLs of 10-week-old C57BL/6J female mice (N = 75) were injured in vivo with the contralateral ACLs serving as controls. Mice were euthanized at 1, 3, 7, 14, or 28 days after injury (n = 12/cohort). Downstream analyses included volumetric cortical and trabecular bone analyses and histopathologic assessments of the knee joint after injury. Gait analyses across all time points were also performed (n = 15 mice). Results: The majority of the ACL injuries in mice were partial tears. The femoral and tibial cortical bone volumes were 39% and 32% lower, respectively, at 28 days after injury than those of the uninjured contralateral knees (P < .01). Trabecular bone measures demonstrated little difference between injured and control knees after injury. Across all bone measures, bone loss was similar between the injured knee condyles and ACL entheses. There was also significant inflammatory activity within the knee after injury. By 7 days after injury, synovitis and fibrosis were sigificantly elevated in the injured knee compared with the controls (P < .01), which corresponded with significantly higher osteoclast activity in bone at this time point compared with the controls. This inflammatory response signficantly persisted throughout the duration of the study (P < .01). The hindlimb gait after injury deviated from normal, but mice habitually loaded their injured knee throughout the study. Conclusion: Bone loss was acute and persisted for 4 weeks after injury in mice. However, the authors' hypothesis was not confirmed, as bone quality was not significantly lower in the entheses compared with the condylar bone regions after injury. With relatively normal hindlimb loading but a significant physiological response after injury, bone loss in this model may be driven by inflammation. Clinical relevance: There is persistent bone resorption and fibrotic tissue development after injury that is not resolved. Inflammatory and catabolic activity may have a significant role in the postinjury decline of bone quality in the knee.
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    Alveolar bone protection by targeting the SH3BP2-SYK axis in osteoclasts
    (Wiley, 2020-02) Kittaka, Mizuho; Yoshimoto, Tetsuya; Schlosser, Collin; Rottapel, Robert; Kajiya, Mikihito; Kurihara, Hidemi; Reichenberger, Ernst J.; Ueki, Yasuyoshi; Biomedical Sciences and Comprehensive Care, School of Dentistry
    Periodontitis is a bacterially induced chronic inflammatory condition of the oral cavity where tooth-supporting tissues including alveolar bone are destructed. Previously, we have shown that the adaptor protein SH3-domain binding protein 2 (SH3BP2) plays a critical role in inflammatory response and osteoclastogenesis of myeloid lineage cells through spleen tyrosine kinase (SYK). In this study, we show that SH3BP2 is a novel regulator for alveolar bone resorption in periodontitis. Micro-CT analysis of SH3BP2-deficient (Sh3bp2 -/- ) mice challenged with ligature-induced periodontitis revealed that Sh3bp2 -/- mice develop decreased alveolar bone loss (male 14.9% ± 10.2%; female 19.0% ± 6.0%) compared with wild-type control mice (male 25.3% ± 5.8%; female 30.8% ± 5.8%). Lack of SH3BP2 did not change the inflammatory cytokine expression and osteoclast induction. Conditional knockout of SH3BP2 and SYK in myeloid lineage cells with LysM-Cre mice recapitulated the reduced bone loss without affecting both inflammatory cytokine expression and osteoclast induction, suggesting that the SH3BP2-SYK axis plays a key role in regulating alveolar bone loss by mechanisms that regulate the bone-resorbing function of osteoclasts rather than differentiation. Administration of a new SYK inhibitor GS-9973 before or after periodontitis induction reduced bone resorption without affecting inflammatory reaction in gingival tissues. In vitro, GS-9973 treatment of bone marrow-derived M-CSF-dependent macrophages suppressed tartrate-resistant acid phosphatase (TRAP)-positive osteoclast formation with decreased mineral resorption capacity even when GS-9973 was added after RANKL stimulation. Thus, the data suggest that SH3BP2-SYK is a novel signaling axis for regulating alveolar bone loss in periodontitis and that SYK can be a potential therapeutic target to suppress alveolar bone resorption in periodontal diseases.
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    Contribution of Porphyromonas gingivalis lipopolysaccharide to experimental periodontitis in relation to aging
    (Springer, 2021) Akkaoui, Juliet; Yamada, Chiaki; Duarte, Carolina; Ho, Anny; Vardar-Sengul, Saynur; Kawai, Toshihisa; Movila, Alexandru; Biomedical and Applied Sciences, School of Dentistry
    Aging is associated with increased prevalence and severity of pathogenic outcomes of periodontal disease, including soft tissue degeneration and bone loss around the teeth. Although lipopolysaccharide (LPS) derived from the key periodontal pathogen Porphyromonas gingivalis (Pg) plays an important role in the promotion of inflammation and osteoclastogenesis via toll-like receptor (TLR)4 signaling, its pathophysiological role in age-associated periodontitis remains unclear. This study investigated the possible effects of Pg-LPS on RANKL-primed osteoclastogenesis and ligature-induced periodontitis in relation to aging using young (2 months old) and aged (24 months old) mice. To the best of our knowledge, our results indicated that expression of TLR4 was significantly diminished on the surface of osteoclast precursors isolated from aged mice compared with that of young mice. Furthermore, our data demonstrated that the TLR4 antagonist (TAK242) dramatically decreased the numbers of tartrate-resistant acid phosphatase positive (TRAP+) osteoclasts differentiated from RANKL-primed young osteoclast precursors (OCPs) compared with those isolated from aged mice in response to Pg-LPS. In addition, using a ligature-induced periodontitis mouse model, we demonstrated that Pg-LPS elevated (1) secretion of senescence-associated secretory phenotype (SASP) markers, including the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β, as well as osteoclastogenic RANKL, and (2) the number of OCPs and TRAP+ osteoclasts in the periodontal lesion induced in young mice. In contrast, Pg-LPS had little, or no, effect on the promotion of periodontitis inflammation induced in aged mice. Altogether, these results indicated that periodontal disease in older mice occurs in a manner independent of canonical signaling elicited by the Pg-LPS/TLR4 axis.
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    Interspecies Comparison of Alveolar Bone Biology, Part I: Morphology and Physiology of Pristine Bone
    (Sage, 2021) Pilawski, I.; Tulu, U. S.; Ticha, P.; Schüpbach, P.; Traxler, H.; Xu, Q.; Pan, J.; Coyac, B. R.; Yuan, X.; Tian, Y.; Liu, Y.; Chen, J.; Erdogan, Y.; Arioka, M.; Armaro, M.; Wu, M.; Brunski, J. B.; Helms, J. A.; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Introduction: Few interspecies comparisons of alveolar bone have been documented, and this knowledge gap raises questions about which animal models most accurately represent human dental conditions or responses to surgical interventions. Objectives: The objective of this study was to employ state-of-the-art quantitative metrics to directly assess and compare the structural and functional characteristics of alveolar bone among humans, mini pigs, rats, and mice. Methods: The same anatomic location (i.e., the posterior maxillae) was analyzed in all species via micro-computed tomographic imaging, followed by quantitative analyses, coupled with histology and immunohistochemistry. Bone remodeling was evaluated with alkaline phosphatase activity and tartrate-resistant acid phosphatase staining to identify osteoblast and osteoclast activities. In vivo fluorochrome labeling was used as a means to assess mineral apposition rates. Results: Collectively, these analyses demonstrated that bone volume differed among the species, while bone mineral density was equal. All species showed a similar density of alveolar osteocytes, with a highly conserved pattern of collagen organization. Collagen maturation was equal among mouse, rat, and mini pig. Bone remodeling was a shared feature among the species, with morphologically indistinguishable hemiosteonal appearances, osteocytic perilacunar remodeling, and similar mineral apposition rates in alveolar bone. Conclusions: Our analyses demonstrated equivalencies among the 4 species in a plurality of the biological features of alveolar bone. Despite contradictory results from older studies, we found no evidence for the superiority of pig models over rodent models in representing human bone biology. Knowledge transfer statement: Animal models are extensively used to evaluate bone tissue engineering strategies, yet there are few state-of-the-art studies that rigorously compare and quantify the factors influencing selection of a given animal model. Consequently, there is an urgent need to assess preclinical animal models for their predictive value to dental research. Our article addresses this knowledge gap and, in doing so, provides a foundation for more effective standardization among animal models commonly used in dentistry.
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    The Utility of AI in Writing a Scientific Review Article on the Impacts of COVID-19 on Musculoskeletal Health
    (Springer, 2024) Awosanya, Olatundun D.; Harris, Alexander; Creecy, Amy; Qiao, Xian; Toepp, Angela J.; McCune, Thomas; Kacena, Melissa A.; Ozanne, Marie V.; Orthopaedic Surgery, School of Medicine
    Purpose of review: There were two primary purposes to our reviews. First, to provide an update to the scientific community about the impacts of COVID-19 on musculoskeletal health. Second, was to determine the value of using a large language model, ChatGPT 4.0, in the process of writing a scientific review article. To accomplish these objectives, we originally set out to write three review articles on the topic using different methods to produce the initial drafts of the review articles. The first review article was written in the traditional manner by humans, the second was to be written exclusively using ChatGPT (AI-only or AIO), and the third approach was to input the outline and references selected by humans from approach 1 into ChatGPT, using the AI to assist in completing the writing (AI-assisted or AIA). All review articles were extensively fact-checked and edited by all co-authors leading to the final drafts of the manuscripts, which were significantly different from the initial drafts. Recent findings: Unfortunately, during this process, it became clear that approach 2 was not feasible for a very recent topic like COVID-19 as at the time, ChatGPT 4.0 had a cutoff date of September 2021 and all articles published after this date had to be provided to ChatGPT, making approaches 2 and 3 virtually identical. Therefore, only two approaches and two review articles were written (human and AI-assisted). Here we found that the human-only approach took less time to complete than the AI-assisted approach. This was largely due to the number of hours required to fact-check and edit the AI-assisted manuscript. Of note, the AI-assisted approach resulted in inaccurate attributions of references (about 20%) and had a higher similarity index suggesting an increased risk of plagiarism. The main aim of this project was to determine whether the use of AI could improve the process of writing a scientific review article. Based on our experience, with the current state of technology, it would not be advised to solely use AI to write a scientific review article, especially on a recent topic.
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    Use of AI Language Engine ChatGPT 4.0 to Write a Scientific Review Article Examining the Intersection of Alzheimer's Disease and Bone
    (Springer, 2024) Margetts, Tyler J.; Karnik, Sonali J.; Wang, Hannah S.; Plotkin, Lilian I.; Oblak, Adrian L.; Fehrenbacher, Jill C.; Kacena, Melissa A.; Movila, Alexandru; Orthopaedic Surgery, School of Medicine
    Purpose of review: This Comment represents three review articles on the relationship between Alzheimer's disease, osteoporosis, and fracture in an exploration of the benefits that AI can provide in scientific writing. The first drafts of the articles were written (1) entirely by humans; (2) entirely by ChatGPT 4.0 (AI-only or AIO); and (3) by humans and ChatGPT 4.0 whereby humans selected literature references, but ChatGPT 4.0 completed the writing (AI-assisted or AIA). Importantly, each review article was edited and carefully checked for accuracy by all co-authors resulting in a final manuscript which was significantly different from the original draft. Recent findings: The human-written article took the most time from start to finish, the AI-only article took the least time, and the AI-assisted article fell between the two. When comparing first drafts to final drafts, the AI-only and AI-assisted articles had higher percentages of different text than the human article. The AI-only paper had a higher percentage of incorrect references in the first draft than the AI-assisted paper. The first draft of the AI-assisted article had a higher similarity score than the other two articles when examined by plagiarism identification software. This writing experiment used time tracking, human editing, and comparison software to examine the benefits and risks of using AI to assist in scientific writing. It showed that while AI may reduce total writing time, hallucinations and plagiarism were prevalent issues with this method and human editing was still necessary to ensure accuracy.