Bone最新文献

{"title":"Exposure to fluoride and risk of primary bone cancer: A systematic review","authors":"Natalie Hajduga ,&nbsp;Murali Perumbakkam Subramanian ,&nbsp;Hannah Brown ,&nbsp;Richard McNally ,&nbsp;Vida Zohoori ,&nbsp;Vikki Rand","doi":"10.1016/j.bone.2024.117320","DOIUrl":"10.1016/j.bone.2024.117320","url":null,"abstract":"<div><div>Fluoride has long been considered essential in the prevention of dental caries, however, its relationship with bone cancer remains unclear. With little improvements in survival from primary bone cancers, it is important to understand the underlying drivers. The focus of this systematic review was, therefore, to assess the association between fluoride exposure and the development of primary bone cancer. The review was conducted as per the PRISMA guidelines and was registered on PROSPERO (CRD42021296109) with a search cut-off of March 2024. In total, 14 studies, involving 8680 participants across all age groups, were identified examining the effects of fluoride exposure on humans investigated for primary bone cancer. Of the 14 studies, only two reported a positive association between fluoride and primary bone cancer. One study including 88 participants reported a positive association between water fluoridation and osteosarcoma development (in young males between 0 and 20 years of age), and the second study, with an unreported number of participants, reported this positive association with bone cancers in males. No association between fluoridation and bone cancer development was reported in the remaining studies. Across all 14 studies, data was presented in a narrative synthesis with subgroup analysis conducted on study design, age, sex, fluoride level and quality score. Both studies reporting a positive association between fluoride and bone cancer identified this association in males, however, both studies concluded that further research is needed. Here we report the most comprehensive systematic review to date examining associations between fluoride exposure and primary bone cancer. We also highlight some of the methodological limitations of some studies, and identify the need, and opportunity, to conduct a large, prospective study to address this and other health issues associated with fluoride.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117320"},"PeriodicalIF":3.5,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of the PGAM5-CypD mitochondrial pathway in methylglyoxal-induced bone loss in diabetic osteoporosis","authors":"Wanying Jiang ,&nbsp;Xinyi Ma ,&nbsp;Bin Li ,&nbsp;Tianle Jiang ,&nbsp;Haopu Jiang ,&nbsp;Wenxia Chen ,&nbsp;Jia Gao ,&nbsp;Yixin Mao ,&nbsp;Xiaoyu Sun ,&nbsp;Zhou Ye ,&nbsp;Shufan Zhao ,&nbsp;Shengbin Huang ,&nbsp;Yang Chen","doi":"10.1016/j.bone.2024.117322","DOIUrl":"10.1016/j.bone.2024.117322","url":null,"abstract":"<div><div>Diabetic osteoporosis (DOP) is a skeletal complication with a high rate of disability. It results in a great burden to the patient's family and society. Methylglyoxal (MG) is a toxic by-product of the glycolytic process that occurs during diabetic conditions. It causes osteoblastic injury and con-tributes to the initiation and development of DOP. Disruption of mitochondrial homeostasis has been implicated as a cause of dysregulated osteo-blastogenesis, an essential step in bone formation. It is unclear whether mitochondrial dysfunction is involved in MG-induced osteoblast dysfunction. In this study, we showed that mitochondrial dysfunction contributes to MG-induced MC3T3-E1 cell apoptosis and impaired differentiation. A significant reduction of mitochondrial membrane potential (MMP) and ATP production occurred in MG-induced osteoblasts as well as increasing mitochondrial reactive oxygen species (mtROS) and intracellular Ca²⁺. Classical antioxidant N-Acetylcysteine (NAC) significantly attenuated mitochondrial dysfunction as well as osteoblast apoptosis and osteogenic differentiation damage induced by MG. More importantly, we found that activating phosphoglycerate mutase family member 5 (PGAM5) and cyclophilin D (CypD), which contributes to mitochondrial homeostasis, is involved in MG-induced osteoblast injury. Both PGAM5 and CypD knockdown effectively reversed osteoblast viability and function, whereas PGAM5 or CypD overexpression aggravated osteoblast injury caused by MG. Moreover, the result of co-transfection revealed that PGAM5 is an upstream signaling molecule of CypD. By constructing type I diabetes mouse models, we further found that the expression of PGAM5 and CypD were both increased in the femur along with a reduction of ATP and increased TUNEL-positive cells. These results, for the first time, suggest that MG-induced mitochondrial dysfunction induces osteoblast injury through the PGAM5-CypD pathway. This study provides insight into the prevention and treatment of DOP.</div></div><div><h3>Lay summary</h3><div>This study highlights the role of mitochondria in regulating osteoblast viability and function under conditions of diabetic osteoporosis (DOP). We found that the PGAM5-CypD mitochondrial pathway is activated following glycolytic by-product methylglyoxal (MG) treatment, which contributes to mitochondrial dysfunction and osteogenic dysfunction. This mechanism implicates mitochondria as a potential therapeutic target for osteoporosis.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117322"},"PeriodicalIF":3.5,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles from mouse bone marrow macrophages-derived osteoclasts treated with zoledronic acid contain miR-146a-5p and miR-322-3p, which inhibit osteoclast function","authors":"Sakura Minami ,&nbsp;Yasuyuki Fujii ,&nbsp;Yusuke Yoshioka ,&nbsp;Ayano Hatori ,&nbsp;Kotaro Kaneko ,&nbsp;Takahiro Ochiya ,&nbsp;Daichi Chikazu","doi":"10.1016/j.bone.2024.117323","DOIUrl":"10.1016/j.bone.2024.117323","url":null,"abstract":"<div><div>Medication-related osteonecrosis of the jaw (MRONJ) is an intractable form of osteonecrosis of the jaw that rarely occurs in patients using bone resorption inhibitors such as bisphosphonates (BPs). Then, extracellular vesicles (EVs) carry various signaling molecules, such as mRNAs, microRNAs (miRNAs), and proteins, and have attracted attention as intercellular communication tools. Recently, the role of EVs in communication between osteoclasts and surrounding bone cells has been confirmed. This study aimed to elucidate the effects of EVs derived from osteoclasts treated with zoledronic acid (ZA), one of the BPs on osteoclast function. EVs were isolated by ultracentrifugation of the culture supernatant of osteoclasts treated with ZA, and miRNAs were extracted from these EVs. Tartrate-resistant acid phosphatase staining of the ZA treated osteoclasts showed reduced osteoclastogenesis. In addition, pit assay showed that ZA significantly decreased the bone resorption capacity of osteoclasts. miRNA-seq analysis identified 11 upregulated and 5 downregulated differentially expressed genes (DEGs) in the miRNA of EVs derived from ZA-treated osteoclasts compared to EVs derived from osteoclasts not treated with ZA. qRT-PCR analysis confirmed the amount of these specific miRNAs, with miR-146a-5p, and miR-322-3p being significantly upregulated by ZA. Overexpression of miR-146a-5p in osteoclasts inhibited osteoclastogenesis and decreased the mRNA expression of osteoclast markers. In addition, <em>Traf6</em> was identified as a candidate target gene of miR-146a-5p in several miRNA databases. Indeed, the overexpression of miR-146a-5p decreased the expression level of <em>Traf6</em> in osteoclasts. Additionally, overexpression of miR-322-3p in the pre-osteoblast, MC3T3-E1 cells, resulted in a significant increase in the mRNA expression levels of <em>Sp7</em>. Our data indicate that BPs attenuate osteoclastogenesis by simultaneously altering the characteristics of osteoclast-derived EVs. Overexpression of miR-146a-5p and miR-322-3p influences osteoclast differentiation, and <em>Traf6</em> is a target gene of miR-146a-5p. On the other hand, Overexpression of miR-322-3p affects osteoblast differentiation. We suggest that ZA-treated osteoclast-derived EVs may play an important role in osteoclast function and bone resorption.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117323"},"PeriodicalIF":3.5,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomimetic periosteum-bone scaffolds with codelivery of BMP-2 and PDGF-BB for skull repair","authors":"Zihao Zhan ,&nbsp;Ran Li ,&nbsp;Yiang Wu ,&nbsp;Xiaotian Shen ,&nbsp;Dongming Fu ,&nbsp;Hao Han ,&nbsp;Pengrui Jing ,&nbsp;Bin Li ,&nbsp;Fengxuan Han ,&nbsp;Bin Meng","doi":"10.1016/j.bone.2024.117315","DOIUrl":"10.1016/j.bone.2024.117315","url":null,"abstract":"<div><div>Tissue engineering employs the use of bioactive materials to facilitate the filling and acceleration of bone defect healing, thereby introducing novel concepts to the field of <em>in situ</em> bone repair. Some studies have shown that periosteum plays an important role in bone regeneration and repair. In this study, biomimetic periosteum-bone scaffolds were prepared by depositing poly-L-lactic acid (PLLA) electrospun fibers on the surface of the gelatin/chitosan cryogel to mimic the bone and periosteum structure, respectively. To improve the bioactivity of the scaffold, bone morphogenetic protein-2 (BMP-2) was loaded into a loose porous mesh-like cryogel, while platelet-derived growth factor-BB (PDGF-BB) was encapsulated in the core of PLLA nanofibers with core-shell structure. Both of these two growth factors were released locally at the site of bone defect, where they exert a synergistic effect on osteogenesis, thereby greatly accelerating bone healing. The <em>in vitro</em> experiments demonstrated that the biomimetic periosteum-bone scaffolds exhibited favourable biocompatibility and osteogenesis ability. Furthermore, the <em>in vivo</em> experiments indicated that the composite scaffold repaired rat skull defects in a more rapid and effective manner. In conclusion, biomimetic periosteum-bone scaffolds with codelivery of BMP-2 and PDGF-BB shows significant potential for bone regeneration.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117315"},"PeriodicalIF":3.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrin α2β1 deficiency enhances osteogenesis via BMP-2 signaling for accelerated fracture repair","authors":"Daniel Kronenberg ,&nbsp;Melanie Brand ,&nbsp;Jens Everding ,&nbsp;Louisa Wendler ,&nbsp;Eric Kieselhorst ,&nbsp;Melanie Timmen ,&nbsp;Michael D. Hülskamp ,&nbsp;Richard Stange","doi":"10.1016/j.bone.2024.117318","DOIUrl":"10.1016/j.bone.2024.117318","url":null,"abstract":"<div><div>Previous studies have shown that the absence of the collagen-binding integrin α2β1 confers protection against osteoporosis, primarily by enhancing osteoblast-mediated matrix formation, with a particular increase in collagen type I production. This study aimed to elucidate the mechanism underlying this increased matrix production. Our findings demonstrate that osteoblasts lacking integrin α2 secrete a pro-osteogenic factor that activates both TGF-β and BMP signaling pathways. Among these, BMP-2 was identified as the key signaling protein responsible for this effect, as its expression was significantly upregulated during osteoblast differentiation. Moreover, integrin α2 deficiency led to earlier and elevated BMP-2 secretion at the cell surface during osteogenesis, which promoted accelerated osteoblast differentiation. This phenomenon likely contributes to enhanced matrix production in aging animals, providing a protective effect against osteoporosis.</div><div>To explore the broader implications of this phenotype, we utilized a fracture healing model. In integrin α2-deficient 12 weeks old female mice, elevated serum levels of BMP-2 were detected during the early stages of fracture repair. This upregulation of BMP signaling within the fracture callus accelerated the healing process, resulting in faster formation and mineralization of the cartilaginous callus. Additionally, the elevated BMP-2 levels facilitated earlier differentiation of chondrocytic cells, evidenced by the premature appearance of collagen type II- and type X-positive cells during endochondral ossification. Despite the accelerated healing, the overall biomechanical integrity of the repaired fractures remained uncompromised.</div><div>Thus, the modulation of integrin α2β1 presents a promising therapeutic target for enhancing fracture repair by regulating BMP-2 signaling in a physiologically relevant manner.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117318"},"PeriodicalIF":3.5,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteoprotegerin secretion and its inhibition by RANKL in osteoblastic cells visualized using bioluminescence imaging","authors":"Hotsuna Ninomiya ,&nbsp;Shinji Fukuda ,&nbsp;Hisayo Nishida-Fukuda ,&nbsp;Yuto Shibata ,&nbsp;Takuma Sato ,&nbsp;Yuko Nakamichi ,&nbsp;Midori Nakamura ,&nbsp;Nobuyuki Udagawa ,&nbsp;Ken Miyazawa ,&nbsp;Takahiro Suzuki","doi":"10.1016/j.bone.2024.117319","DOIUrl":"10.1016/j.bone.2024.117319","url":null,"abstract":"<div><div>Bone remodeling is regulated by the interaction between receptor activator of nuclear factor kappa-B ligand (RANKL) and its receptor RANK on osteoblasts and osteoclasts, respectively. Osteoprotegerin (OPG) is secreted from osteoblasts and inhibits osteoclast differentiation by acting as a decoy receptor for RANKL. Despite its importance, the mechanism underlying the secretion of OPG remains poorly understood. Here, we applied a method of video-rate bioluminescence imaging using a fusion protein with <em>Gaussia</em> luciferase (GLase) and visualized the secretion of OPG from living mouse osteoblastic MC3T3-E1 cells. The bioluminescence imaging revealed that the secretion of OPG fused to GLase (OPG-GLase) occurred frequently and widely across the cell surface. Notably, co-expression of RANKL significantly reduced the secretion of OPG-GLase, indicating an inhibitory role of RANKL on OPG secretion within cells. Further imaging and biochemical analyses using deletion mutants of OPG and RANKL, as well as RANKL mutants that cause autosomal recessive osteopetrosis, demonstrated the essential role of protein-protein interaction between OPG and RANKL in the inhibition of OPG secretion. Treatment with proteasome inhibitors resulted in increased levels of OPG in both culture medium and cell lysates. However, the fold-increase of OPG was similar regardless of the presence or absence of RANKL, suggesting that the regulation of OPG secretion by RANKL is independent of proteasome activity. This report visualized the secretion of OPG from living cells and provided evidence for a novel intracellular inhibitory effect of RANKL on OPG secretion.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"191 ","pages":"Article 117319"},"PeriodicalIF":3.5,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HarDNet-based deep learning model for osteoporosis screening and bone mineral density inference from hand radiographs","authors":"Chan-Shien Ho ,&nbsp;Tzuo-Yau Fan ,&nbsp;Chang-Fu Kuo ,&nbsp;Tzu-Yun Yen ,&nbsp;Szu-Yi Chang ,&nbsp;Yu-Cheng Pei ,&nbsp;Yueh-Peng Chen","doi":"10.1016/j.bone.2024.117317","DOIUrl":"10.1016/j.bone.2024.117317","url":null,"abstract":"<div><h3>Purpose</h3><div>Osteoporosis, affecting over 200 million individuals, often remains unrecognized and untreated, increasing the risk of fractures in older adults. Osteoporosis is typically diagnosed with bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA). This study aims to develop DeepDXA-Hand, a deep learning model using the efficient CNN-based deep learning architecture, for opportunistic osteoporosis screening from hand radiographs.</div></div><div><h3>Methods</h3><div>DeepDXA-Hand utilizes a CNN-based, HarDNet, approach to predict BMD non-invasively. A total of 10,351 hand radiographs and DXA pairs were used for model training and validation. The model's interpretability was enhanced using GradCAM for hotspot analysis to determine the model's attention areas.</div></div><div><h3>Results</h3><div>The predicted and ground truth BMD were significantly correlated with a correlation coefficient of 0.745. For binary classification of osteoporosis, DeepDXA-Hand demonstrated a sensitivity of 0.73, specificity of 0.83, and accuracy of 0.80, indicating its clinical potential. The model mainly focused on the carpal bones, such as the capitate, trapezoid, hamate, triquetrum, and the head of the second metacarpal bone, suggesting these areas provide radiological features for inferring BMD.</div></div><div><h3>Conclusion</h3><div>DeepDXA-Hand shows potential for the early detection of osteoporosis with high sensitivity and specificity. Further studies should explore its utility in predicting fracture risks.</div></div><div><h3>Mini abstract</h3><div>Osteoporosis affects millions and often goes undetected and untreated. DeepDXA-Hand, a HarDNet-based deep learning model, predicted bone mineral density with a correlation of 0.745 and classified osteoporosis with 0.80 accuracy. This model enhances early detection and has significant clinical potential as osteoporosis opportunistic screening tool.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117317"},"PeriodicalIF":3.5,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Teriparatide administration is osteoanabolic but does not impact atherosclerotic plaque calcification and progression in a mouse model of menopause","authors":"Laurence Bessueille ,&nbsp;Anne Briolay ,&nbsp;Nicolas Guillot ,&nbsp;Saïda Mebarek ,&nbsp;Solène Viallon ,&nbsp;Norbert Laroche ,&nbsp;Marie-Hélène Lafage-Proust ,&nbsp;David Magne","doi":"10.1016/j.bone.2024.117316","DOIUrl":"10.1016/j.bone.2024.117316","url":null,"abstract":"<div><div>Menopause exacerbates osteoporosis and increases the risk of atherosclerotic plaque rupture, leading to cardiovascular mortality. Osteoporotic women are increasingly treated with teriparatide (TPTD, 1–34 parathyroid hormone), one of the few treatments that stimulate bone formation. Despite the fact that atherosclerotic plaque calcification is a hallmark of plaque development, the impact of TPTD administration on plaque calcification remain unclear. In this context, we sought to determine the effects of TPTD administration on atherosclerosis in ovariectomized (OVX) apolipoprotein E deficient mice (<em>ApoE</em>^−/−), as a model of postmenopausal osteoporosis. OVX <em>ApoE</em>^−/− mice, fed a high fat, high cholesterol diet to induce atherosclerosis, received either vehicle or TPTD daily injections (40 μg/kg/d) for 4 or 10 weeks, at which points plaques are respectively weakly and heavily calcified. After sacrifice, bone remodeling was evaluated by serum markers and bone histomorphometry. Bone architectural parameters were measured by μCT. Aortic plaques were analyzed histologically, and their calcification with von Kossa staining and the calcium tracer Osteosense. Plaque inflammation and calcification markers were measured by RT-qPCR. Intermittent TPTD increased bone volume in OVX mice, due to a higher stimulation of bone formation relatively to bone resorption. These effects were not accompanied by changes in serum levels of cholesterol, triglycerides, glucose or insulin. TPTD neither significantly affected aortic plaque size, inflammation, and calcification, even if it slightly increased vascular smooth muscle cell transdifferentiation into calcifying cells. In conclusion, TPTD exhibits osteoanabolic effects in OVX <em>ApoE</em>^−/− mice, without significantly influencing atherosclerotic plaque progression or calcification in the short term.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117316"},"PeriodicalIF":3.5,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise-induced interactions between skeletal muscle and bone via myokines and osteokine in mice: Role of FNDC5/irisin, IGF-1, and osteocalcin","authors":"Junpei Hatakeyama ,&nbsp;Shota Inoue ,&nbsp;Hanlin Jiang ,&nbsp;Ryo Yokoi ,&nbsp;Hideki Moriyama","doi":"10.1016/j.bone.2024.117314","DOIUrl":"10.1016/j.bone.2024.117314","url":null,"abstract":"<div><div>Skeletal muscle and bone interact to maintain their structure and function. Physical exercise is the most effective and easily applicable strategy to maintain their functions; however, exercise-induced interactions by soluble factors remained elusive. Our study aimed to identify exercise-induced interactions between muscle and bone by examining (1) the effects of myokine on bone and (2) the effects of osteocalcin (OCN) on skeletal muscle. To understand the effects of exercise-induced myokines on bone, we examined the effects of FNDC5 for aerobic exercise and IGF-1 for resistance exercise using a muscle-specific myokine overexpression model. To examine OCN effects on muscle, mice were intraperitoneally administered OCN-neutralizing antibody during long-term exercise. Our result showed that aerobic exercise tended to increase serum HA-tag protein attached to FNDC5 in muscle-specific overexpression groups. In addition, osteoblastic activation was increased only after aerobic exercise with HA/FNDC5 overexpression. Resistance exercise did not alter circulating HA-tag (muscle-derived IGF-1) and bone metabolism after IGF-1/HA overexpression. In the OCN study, aerobic exercise enhanced endurance capacity by restoring muscle glycogen content; however, OCN neutralization returned these to baseline. After resistance exercise, OCN suppression inhibited muscle hypertrophy and strength gains by preventing protein synthesis. Our results suggest that aerobic exercise following FNDC5 muscle overexpression promotes osteoblast activity, which may be partially caused by muscle-derived FNDC5 secretion. In addition, OCN was necessary for muscle adaptation in both aerobic and resistance exercises.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117314"},"PeriodicalIF":3.5,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carbonic anhydrase 2 is important for articular chondrocyte function and metabolic homeostasis","authors":"Mingming Yan ,&nbsp;Lei Cai ,&nbsp;Xin Duan ,&nbsp;Eric D. Tycksen ,&nbsp;Muhammad Farooq Rai","doi":"10.1016/j.bone.2024.117313","DOIUrl":"10.1016/j.bone.2024.117313","url":null,"abstract":"<div><h3>Objectives</h3><div>Aberrant chondrocyte metabolism significantly contributes to cartilage degeneration and osteoarthritis (OA) genesis. However, the mechanisms driving the metabolic shift in OA chondrocytes remain unclear. Interestingly, carbonic anhydrase 2 (CA2) is implicated in metabolic regulation, and its expression dramatically increases in OA chondrocytes, but its exact role and mechanism are poorly understood. This study investigates the mechanistic role of CA2 in chondrocyte metabolic homeostasis under hypoxic and inflammatory conditions.</div></div><div><h3>Methods</h3><div>RNA-seq was performed on CA2-deficient C28/I2 cells to identify pathways affected by the loss of CA2 function. We examined CA2’s impact on chondrocyte metabolism, anabolism, and catabolism using C28/I2 cells and primary chondrocytes under normoxia and hypoxia and in a model of inflammatory OA.</div></div><div><h3>Results</h3><div>RNA-seq revealed enrichment of glycolysis, apoptosis, and TNF signaling pathways in CA2-deficient cells. Under hypoxia, CA2 expression increased 10-fold in a HIF-1α-independent manner. Knockdown of CA2 reduced extracellular lactate production, increased ADP/ATP ratio, impaired glycolysis, reduced glycolytic capacity, and lowered expression of glycolysis rate-limiting enzymes but did not disrupt pH_i and ROS production. CA2 deficiency altered chondrocyte anabolic and catabolic equilibrium by affecting PI3K/AKT and RELA/p65 signaling. CA2-deficient chondrocytes displayed impeded migration, suppressed proliferation, and cell cycle arrest at the G0/G1 phase. Forced expression of CA2 stabilized chondrocyte metabolism and restored cellular functions.</div></div><div><h3>Conclusions</h3><div>Our research uncovered a hitherto unknown mechanistic role for CA2 in regulating chondrocyte energy metabolism and inflammation, underscoring its potential as a critical mediator in OA pathogenesis. Further research using a murine model of experimental OA is warranted to capture the functional implications of CA2.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117313"},"PeriodicalIF":3.5,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}