Ask about this productRelated genes to: IFT88 antibody
- Gene:
- IFT88 NIH gene
- Name:
- intraflagellar transport 88
- Previous symbol:
- TTC10
- Synonyms:
- hTg737, Tg737, D13S1056E, MGC26259
- Chromosome:
- 13q12.11
- Locus Type:
- gene with protein product
- Date approved:
- 2004-04-16
- Date modifiied:
- 2016-10-05
Related products to: IFT88 antibody
Related articles to: IFT88 antibody
- Neutralizing sclerostin antibodies (Scl-Ab) mitigate bone loss and promote bone formation to address fracture risk in postmenopausal osteoporosis. Clinically, this treatment is administered monthly for women at high risk of fragility fractures, who are often years into menopause. Preclinical studies have demonstrated that dampening of bone formation occurs with continuous dosing at supraphysiological doses. Osteoporotic bone loss occurs rapidly during early menopause, followed by longer-term changes in bone mineralization and osteocyte activity. Whether earlier administration of lower-exposure Scl-Ab can mitigate bone loss and osteocyte-mediated mineralization is unknown. The objective of this study was to evaluate the effects of early intermittent low-dose Scl-Ab on: (1) osteoclastogenesis and bone resorption, (2) perilacunar remodelling, (3) secondary mineralization, and (4) osteocyte mechanosensitivity. Female retired breeder Wistar rats underwent bilateral ovariectomy and received monthly low-dose Scl-Ab injections (2 mg/kg/month) from 3 to 14 weeks post-OVX, while a control group remained untreated. Early intermittent low-dose Scl-Ab treatment increased bone formation and reduced osteoclastogenesis and catabolic gene expression ((Sost, Ctsk, Mmp9) compared to untreated rats. Treatment also decreased the percentage of empty lacunae and the number of MMP14+ osteocytes, accompanied by lower perilacunar mineral density and smaller lacunar size, indicating improved osteocyte survival and reduced perilacunar remodelling. Conversely, expression of osteocyte-mediated mineralization genes (DMP1, PHEX, OPN, ALP) and mechanotransduction-related genes (Vcl, integrins α5, αV, β1, CX43, Axin2, IFT88, Adcy6, Pkd1, Cav1) were reduced. Together, these findings suggest that early intermittent low-dose Scl-Ab therapy promotes surface bone formation while attenuating osteocyte-mediated mineralization after initial bone loss. - Source: PubMed
Publication date: 2026/04/07
Naqvi Syeda MasoomaAli WahaajAllison HollieO'Sullivan Laura MHoldsworth GillPanadero-Perez Juan AlbertoSchiavi-Tritz JessicaMcNamara Laoise M - Tubulin post-translational modifications confer diverse functions to microtubules, with polyglutamylation representing a dynamic modification governed by coordinated glutamylation and deglutamylation. AGBL5 functions as a deglutamylase that removes glutamate residues at branch points within polyglutamate chains. While pathogenic variants in human are associated with retinitis pigmentosa, the underlying mechanism remains poorly defined. In the present study, an knockout mouse model was established and exhibited pronounced tubulin hyperglutamylation in photoreceptors, followed by progressive retinal degeneration. Transcriptomic profiling identified widespread disruption of ciliary function in knockout mice. Ultrastructural analysis by transmission electron microscopy revealed an impaired inner scaffold within the connecting cilium. Consistent with this defect, key phototransduction proteins were mislocalized or down-regulated in both mutant rod and cone photoreceptors, accompanied by severe disorganization of outer segment disk membranes. Immunofluorescence further demonstrated impaired recruitment of IFT88, kinesin-II, and dynein-2 to the CC, suggesting defective intraflagellar transport. Collectively, these findings indicate that AGBL5-dependent tubulin glutamylation homeostasis is essential for photoreceptor survival through preservation of CC architecture and normal protein trafficking mediated by intraflagellar transport. - Source: PubMed
Publication date: 2026/02/10
Wang Hao-LinWang TingZhen Fang-YuanLin Yong-QiongTong Ying-JieWu Jia-HuiGuo Jia-XinWang Jia-JiaDong Shu-QianJanke CarstenMagiera Maria MZhang Hou-BinZou Tong-Dan - Autosomal-dominant polycystic kidney disease (ADPKD) remains refractory to curative therapy partly due to the lack of human models that recapitulate its adult-onset nature, genetic context, and multi-segment origin. Here, we established expandable, multi-lineage adult renal organoids (MAROs) directly from surgical specimens of ADPKD patients and healthy donors, creating a three-dimensional (3D) high-content screening platform. Patient-derived MAROs faithfully reproduced hallmark cystogenic features, including elongated primary cilia, polarity disruption, and elevated Rho GTPase/planar cell polarity (PCP) signaling. Single-cell transcriptomics of PKD1/PKD2-mutant organoids revealed genotype-specific alterations. Genetic ablation of IFT88 disrupted cilia and selectively attenuated Rho/PCP activity in mutant backgrounds, supporting a cilia-dependent cyst-activating (CDCA) mechanism in cystogenesis. Microfluidic perfusion accelerated cyst expansion and amplified Rho/PCP signaling. A high-throughput drug screen identified Rho GTPase inhibitors, including ML141, as effective cyst-reducing agents across genotypes without compromising viability. Our findings establish a patient-derived organoid platform that captures ADPKD pathology and nominates Rho pathway modulation as a therapeutic strategy. - Source: PubMed
Publication date: 2026/04/06
Guo LiqiangFan YujiaSun HuixianDu HaoranXiong HuiLi YilinZhang XinyanGuan YongRen LingtongWang XuanChen KaiAn YachunZhang XiaohuiMao YunuoGong YongfengKong FengQiu JichuanChen RuiShi BenkangYi FanHu HuiliZhao Shengtian - Primary cilia play a crucial role in the development and mechanosensation of various tissue types, including bone. In this study, we investigated their role in bone growth and adaptation by targeting two cilia specific genes, IFT88 and MKS5. Conditional knockout (cKO) of IFT88 in osteoblasts significantly reduced body weight and femur length in mice compared to the littermate controls. Additionally, female IFT88 cKO mice exhibited a significant suppression of bone formation rate compared to the littermate controls. To further explore the role of primary cilia in osteocytes, osteocytes specific MKS5 cKO mice underwent axial ulnar loading at a peak force of 2.9N for females and 3.2N for males with 120 cycles per day for three consecutive days. Load induced bone formation rate was significantly decreased by 48% in males and 42% in females compared to the littermate control mice. These findings underscore the critical role of primary cilia in bone development and mechano-adaptation. They suggest that functional primary cilia in osteoblasts are essential for skeletal development, while those in osteocytes mediates mechanically induced bone formation, highlighting its potential as therapeutic targets for bone loss prevention. - Source: PubMed
Publication date: 2026/04/02
Moraes de Lima Perini MarianaFayemi Alyssa FPugh Julie NScott Elizabeth MBhula KaranChirgwin AustinWhite Olivia NBerbari Nicolas FLi Jiliang - Heterotopic ossification (HO), the aberrant formation of bone within soft tissues, arises either from rare genetic mutations or more commonly from traumatic insults. It is a major cause of morbidity not only in individuals harboring causative mutations, but also in those undergoing musculoskeletal surgery or trauma and in soldiers sustaining blast or burn injuries. Bone morphogenetic protein (BMP) signaling is a central driver of both hereditary and acquired forms of HO. Primary cilia are nonmotile, antenna-like organelles that extend from the cell surface and serve as crucial sensory and signaling hubs by concentrating key pathway components within a confined volume at the ciliary tip. However, their functional role in the pathogenesis of traumatic HO remains poorly understood. We investigate the role of primary cilia in traumatic HO using a genetically modified mouse model and cellular model. We demonstrate that BMP signaling is attenuated when primary cilia function is disrupted. Both ciliation frequency and ciliary length were reduced in -CreERT2 (-CreERT2;) tenocytes. Deletion of effectively suppressed pathological BMP signaling and inhibited HO formation. These findings establish that functional primary cilia are required for traumatic HO development and highlight ciliary regulation as a potential therapeutic avenue for preventing or mitigating post-traumatic HO. - Source: PubMed
Publication date: 2026/03/19
Yuan XinyuanToutounchi SamanLaw Susan FAchudhan DavidChandra AbhishekHe KaiCao YingshuHu JinghuaPignolo Robert JWang Haitao