Hasil untuk "Diseases of the musculoskeletal system"

Rachael Stovall, Cinthia Blat, Eric Roberts et al.

Objective We examined sex differences in medication discontinuation among patients with axial spondyloarthritis (axSpA) initiating tumor necrosis factor inhibitors (TNFi), interleukin‐17 inhibitors (IL‐17i), or JAK inhibitors (JAKi). Methods Using data from the Rheumatology Informatics System for Effectiveness (RISE) Registry (2003–2025), we assessed medication discontinuation by sex among new users of TNFi, IL‐17i, and JAKi. Cox regression models were used to evaluate associations between sex and treatment discontinuation, adjusting for sociodemographic and clinical factors. We also examined medication continuation by sex and age group (18–64 vs ≥65 years) using Kaplan‐Meier curves and tested for interactions between sex and age, race, and area deprivation index (ADI). Results Among 7,200 individuals, the mean ± SD age was 52.7 ± 14.7 years; 58.3% were female and 68.7% were non‐Hispanic White. Among TNFi users (N = 6,256), women had a 24% higher risk of discontinuation compared to men (hazard ratio [HR]: 1.24; 95% confidence interval [CI]: 1.16–1.32). Among IL‐17i users (n = 693), women had a 25% higher risk of discontinuation (HR: 1.25; 95% CI: 1.01–1.54). No significant sex differences were observed among JAKi users (N = 251). Among TNFi users, women under 65 years had the lowest probability of treatment continuation. There was no statistically significant interaction between sex and age, race or ADI. Conclusions In a large US registry, women with axSpA were more likely to discontinue TNFi and IL‐17i than men. Larger studies with longer follow‐up since treatment approval are needed to confirm the lack of sex differences in JAKi discontinuation as this group could be underpowered.

Ning Kong, Jiankang Hu, Dongzhou Liu et al.

Abstract Introduction Ixekizumab, an interleukin 17A inhibitor, improved the Assessment of SpondyloArthritis international Society 40 (ASAS40) response rates irrespective of baseline inflammation in international populations with radiographic axial spondyloarthritis (r-axSpA). We investigated the association of baseline inflammation (measured by serum C-reactive protein [CRP] levels) with ixekizumab efficacy in Chinese patients with r-axSpA. Methods This was a subgroup analysis of a Chinese phase 3 study. Adults with r-axSpA who were biologic-naïve, or tumor necrosis factor inhibitor-experienced with baseline CRP > 5 mg/l, were randomized (1:1) to receive ixekizumab 80 mg every 4 weeks (IXEQ4W) or placebo, for 16 weeks. The following endpoints were analyzed by normal (≤ 5 mg/l) or elevated (> 5 mg/l) baseline CRP levels: ASAS40; Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI50); Ankylosing Spondylitis Disease Activity Score (ASDAS) < 2.1; ASDAS clinically important improvement (CII; change from baseline ≥ 1.1); ASDAS major improvement (MI; change from baseline ≥ 2.0 or achievement of lowest possible score); Bath Ankylosing Spondylitis Metrology Index (BASMI) linear score; Bath Ankylosing Spondylitis Functional Index (BASFI); Short Form-36 Physical Component Score (SF-36 PCS). Results A total of 147 patients were randomized. At week 16, the ASAS40 response rate was greater with IXEQ4W versus placebo in the normal (50.0% vs. 15.0%; p < 0.05) and elevated (29.5% vs. 5.7%; p < 0.01) CRP subgroups. Significant improvements in BASDAI50 response rate, ASDAS < 2.1, and ASDAS CII with IXEQ4W versus placebo were observed in both subgroups (normal CRP: p < 0.05, p < 0.01, and p < 0.05, respectively; elevated CRP: p < 0.01, p < 0.001, and p < 0.001, respectively); IXEQ4W significantly improved ASDAS MI in the elevated CRP subgroup (p < 0.001). IXEQ4W significantly improved linear BASMI and BASFI scores in the normal CRP subgroup (p < 0.001 and p < 0.01, respectively), while SF-36 PCS improved in both subgroups (both p < 0.05). Conclusions Ixekizumab showed efficacy in Chinese patients with r-axSpA, irrespective of baseline CRP levels, consistent with results in international populations with r-axSpA. Trial Registration ClinicalTrials.gov identifier, NCT04285229.

Yidan Wang, Pengxiao Liu, Zihao Li et al.

Abstract Background Fibromyalgia is a chronic condition marked by widespread pain and various accompanying symptoms. Compared to healthy individuals and other rheumatic disease patients, it leads to more severe symptoms and a lower quality of life. Whether fibromyalgia patients in a mild activity or remission stage still experience core symptoms remains unclear. Objective To compare the severity of clinical symptoms and quality of life (QOL) in patients with remission or mild fibromyalgia (RFM) and remission or low disease activity in rheumatoid arthritis (RRA) patients and healthy controls (HCs) to investigate whether fibromyalgia in a stable stage can be disease-free. Methods This cross-sectional study evaluated a total of 266 RFM and 252 RRA patients and 50 HCs using Revised Fibromyalgia Impact Questionnaire (FIQR), Widespread Pain Index (WPI), Pain Visual Analogue Scale (VAS), Numerical Rating Scale, Multidimensional Fatigue Inventory (MFI-20), Pittsburgh Sleep Quality Index (PSQI), and Beck Depression Inventory (BDI), and Short Form-36 Health Status Questionnaire (SF-36). Results The FIQR total score and pain VAS, MFI, and PSQI scores were higher in RFM and RRA patients compared to HCs (P < 0.001). RFM patients had higher BDI and WPI scores than RRA patients (P < 0.001). The majority of RFM patients (97.4%) had more than two pain sites, with moderate-to-severe pain (78.2%), sleep disorders (85.0%), and depression (53.4%), all of which were significantly higher than those in RRA patients (P < 0.001). RFM patients also had lower scores in SF-36 physical and mental component summaries and subscores for role physical, pain index, general health perception, vitality, and mental health index, but a higher social functioning score than RRA patients (P < 0.001). Conclusion Despite being in a mild activity or remission stage, RFM patients experience more severe symptoms and poorer QOL than RRA patients. Therefore, individualized evaluation and intensive management are required. Trial registration ClinicalTrials.gov Identifier: NCT02449395, registered on May 20, 2015.

Koshiro Sonomoto, Yoshihisa Fujino, Hiroaki Tanaka et al.

Abstract Introduction This study aimed to develop low-cost models using machine learning approaches predicting the achievement of Clinical Disease Activity Index (CDAI) remission 6 months after initiation of tumor necrosis factor inhibitors (TNFi) as primary biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) for rheumatoid arthritis (RA). Methods Data of patients with RA initiating TNFi as first b/tsDMARD after unsuccessful methotrexate treatment were collected from the FIRST registry (August 2003 to October 2022). Baseline characteristics and 6-month CDAI were collected. The analysis used various machine learning approaches including logistic regression with stepwise variable selection, decision tree, support vector machine, and lasso logistic regression (Lasso), with 48 factors accessible in routine clinical practice for the prediction model. Robustness was ensured by k-fold cross validation. Results Among the approaches tested, Lasso showed the advantages in predicting CDAI remission: with a mean area under the curve 0.704, sensitivity 61.7%, and specificity 69.9%. Predicted TNFi responders achieved CDAI remission at an average rate of 53.2%, while only 26.4% of predicted TNFi non-responders achieved remission. Encouragingly, the models generated relied solely on patient-reported outcomes and quantitative parameters, excluding subjective physician input. Conclusions While external cohort validation is warranted for broader applicability, this study highlights the potential for a low-cost predictive model to predict CDAI remission following TNFi treatment. The approach of the study using only baseline data and 6-month CDAI measures, suggests the feasibility of establishing regional cohorts to generate low-cost models tailored to specific regions or institutions. This may facilitate the application of regional/in-house precision medicine strategies in RA management.

Zhenghui Wang, Wenpan Zhu, Guang Li et al.

Abstract Background Adolescent idiopathic scoliosis (AIS) stands as the predominant spinal deformity in adolescents, manifesting symptoms including back pain, functional limitations, cosmetic worries, and respiratory dysfunction. At present, six approaches of scoliosis-specific exercises are globally practiced, encompassing Schroth exercise, the Scientific Exercise Approach to Scoliosis (SEAS), the Dobomed, the side shift exercise, active self-correction, and the Functional Individual Therapy of Scoliosis (FITS). However, there is no systematic review and meta-analysis comparing the efficacy of these six types of scoliosis-specific exercises on adolescent idiopathic scoliosis. Objective To evaluate and compare the efficacy of six types of scoliosis-specific exercises on spinal deformity and quality of life in AIS. Materials and methods A systematic search was performed on PubMed, EMBASE, and the Cochrane Library from their inception to September 2023. Two independent auditors screened all studies according to predefined inclusion and exclusion criteria. Clinical trials were compiled to investigate the effects of six exercise interventions on spinal deformity and quality of life in AIS. Results Twenty-four studies were included, with a sample size of 1069 subjects. After meta-analysis, it was shown that SEAS ranked first in reducing Cobb angles (SUCRA: 84.8%); active self-correction and Schroth significantly improved the angles of trunk rotation in AIS (SUCRA: 86.6% and SUCRA: 79.1%, respectively); active self-correction and Schroth showed significant improvements in quality of life (SUCRA: 76.6% and SUCRA: 76.0%, respectively). Conclusion According to the current findings, active self-correction demonstrated superior short-term benefits compared to other exercise interventions in ameliorating spinal deformity and improving quality of life for adolescents with idiopathic scoliosis. Meanwhile, Schroth exhibited long-term effects in improving both spinal deformity and quality of life. Registration information This review was registered on PROSPERO on June 20, 2023 (ID: CRD42023433152).

Shaojun Xie, Sulbha Choudhari, Chia‐Lung Wu et al.

Abstract The epigenome of stem cells occupies a critical interface between genes and environment, serving to regulate expression through modification by intrinsic and extrinsic factors. We hypothesized that aging and obesity, which represent major risk factors for a variety of diseases, synergistically modify the epigenome of adult adipose stem cells (ASCs). Using integrated RNA‐ and targeted bisulfite‐sequencing in murine ASCs from lean and obese mice at 5‐ and 12‐months of age, we identified global DNA hypomethylation with either aging or obesity, and a synergistic effect of aging combined with obesity. The transcriptome of ASCs in lean mice was relatively stable to the effects of age, but this was not true in obese mice. Functional pathway analyses identified a subset of genes with critical roles in progenitors and in diseases of obesity and aging. Specifically, Mapt, Nr3c2, App , and Ctnnb1 emerged as potential hypomethylated upstream regulators in both aging and obesity (AL vs. YL and AO vs. YO), and App , Ctnnb1, Hipk2, Id2 , and Tp53 exhibited additional effects of aging in obese animals. Furthermore, Foxo3 and Ccnd1 were potential hypermethylated upstream regulators of healthy aging (AL vs. YL), and of the effects of obesity in young animals (YO vs. YL), suggesting that these factors could play a role in accelerated aging with obesity. Finally, we identified candidate driver genes that appeared recurrently in all analyses and comparisons undertaken. Further mechanistic studies are needed to validate the roles of these genes capable of priming ASCs for dysfunction in aging‐ and obesity‐associated pathologies.

Alina D. Schmidt, Charlene Miciano, Qi Zheng et al.

Dongxu Li, Ruichao Cao, Wei Dong et al.

Abstract Objective The aim of this study was to search for key genes in ankylosing spondylitis (AS) through comprehensive bioinformatics analysis, thus providing some theoretical support for future diagnosis and treatment of AS and further research. Methods Gene expression profiles were collected from Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/ ) by searching for the term "ankylosing spondylitis". Ultimately, two microarray datasets (GSE73754 and GSE11886) were downloaded from the GEO database. A bioinformatic approach was used to screen differentially expressed genes and perform functional enrichment analysis to obtain biological functions and signalling pathways associated with the disease. Weighted correlation network analysis (WGCNA) was used to further obtain key genes. Immune infiltration analysis was performed using the CIBERSORT algorithm to conduct a correlation analysis of key genes with immune cells. The GWAS data of AS were analysed to identify the pathogenic regions of key genes in AS. Finally, potential therapeutic agents for AS were predicted using these key genes. Results A total of 7 potential biomarkers were identified: DYSF, BASP1, PYGL, SPI1, C5AR1, ANPEP and SORL1. ROC curves showed good prediction for each gene. T cell, CD4 naïve cell, and neutrophil levels were significantly higher in the disease group than in the paired normal group, and key gene expression was strongly correlated with immune cells. CMap results showed that the expression profiles of ibuprofen, forskolin, bongkrek-acid, and cimaterol showed the most significant negative correlation with the expression profiles of disease perturbations, suggesting that these drugs may play a role in AS treatment. Conclusion The potential biomarkers of AS screened in this study are closely related to the level of immune cell infiltration and play an important role in the immune microenvironment. This may provide help in the clinical diagnosis and treatment of AS and provide new ideas for further research.

Julian Koettnitz, Filippo Migliorini, Christian D. Peterlein et al.

Abstract Introduction Total hip (THA) and knee arthroplasty (TKA) are surgical interventions for patients with primary and posttraumatic osteoarthritis. The present clinical investigation compared gender differences in THA and TKA. Methods Data from 419 patients following primary THA and TKA were collected. The occurrence of systemic and surgery-related complications, the units of blood transfused, and the change in Hb were investigated. Hb was collected preoperatively and at 1, 2, 4 and 7 days postoperatively. Statistical analysis was performed using the software IBM SPSS 28. Results There was no significant difference in surgery-related and general complications in men between THA and TKA. A significant difference between THA and TKA in systemic complications in women was observed. No significant difference between THA and TKA in related to surgery-related complications was evidenced. In men, no difference in Hb progression was observed. In women, a significant Hb drop was evidenced (p = 0.03). The rate of blood transfusion units in women was significantly greater in TKA than in THA (p = 0.001). No statistically significant difference was observed in men in the rate of transfusion between THA and TKA. Conclusion Perioperative care should be organized differently for women and men. Furthermore, a differentiation between the procedures for each sex could prevent the occurrence of perioperative complicated courses.

Hongtao Zhang, Nelson Shi, Zhuo Diao et al.

Wagner S. Dantas, Elizabeth R.M. Zunica, Elizabeth C. Heintz et al.

Abstract Background Sarcopenic obesity is a highly prevalent disease with poor survival and ineffective medical interventions. Mitochondrial dysfunction is purported to be central in the pathogenesis of sarcopenic obesity by impairing both organelle biogenesis and quality control. We have previously identified that a mitochondrial‐targeted furazano[3,4‐b]pyrazine named BAM15 is orally available and selectively lowers respiratory coupling efficiency and protects against diet‐induced obesity in mice. Here, we tested the hypothesis that mitochondrial uncoupling simultaneously attenuates loss of muscle function and weight gain in a mouse model of sarcopenic obesity. Methods Eighty‐week‐old male C57BL/6J mice with obesity were randomized to 10 weeks of high fat diet (CTRL) or BAM15 (BAM15; 0.1% w/w in high fat diet) treatment. Body weight and food intake were measured weekly. Body composition, muscle function, energy expenditure, locomotor activity, and glucose tolerance were determined after treatment. Skeletal muscle was harvested and evaluated for histology, gene expression, protein signalling, and mitochondrial structure and function. Results BAM15 decreased body weight (54.0 ± 2.0 vs. 42.3 ± 1.3 g, P < 0.001) which was attributable to increased energy expenditure (10.1 ± 0.1 vs. 11.3 ± 0.4 kcal/day, P < 0.001). BAM15 increased muscle mass (52.7 ± 0.4 vs. 59.4 ± 1.0%, P < 0.001), strength (91.1 ± 1.3 vs. 124.9 ± 1.2 g, P < 0.0001), and locomotor activity (347.0 ± 14.4 vs. 432.7 ± 32.0 m, P < 0.001). Improvements in physical function were mediated in part by reductions in skeletal muscle inflammation (interleukin 6 and gp130, both P < 0.05), enhanced mitochondrial function, and improved endoplasmic reticulum homeostasis. Specifically, BAM15 activated mitochondrial quality control (PINK1‐ubiquitin binding and LC3II, P < 0.01), increased mitochondrial activity (citrate synthase and complex II activity, all P < 0.05), restricted endoplasmic reticulum (ER) misfolding (decreased oligomer A11 insoluble/soluble ratio, P < 0.0001) while limiting ER stress (decreased PERK signalling, P < 0.0001), apoptotic signalling (decreased cytochrome C release and Caspase‐3/9 activation, all P < 0.001), and muscle protein degradation (decreased 14‐kDa actin fragment insoluble/soluble ratio, P < 0.001). Conclusions Mitochondrial uncoupling by agents such as BAM15 may mitigate age‐related decline in muscle mass and function by molecular and cellular bioenergetic adaptations that confer protection against sarcopenic obesity.

Wen Guo, Hong Wang, Tao Chen et al.

Abstract Background Neuromuscular choristomas (NMCs), are extremely rare developmental lesions that, have been previously established associated with recurrent fibromatosis after surgery, leading to several operations or even amputation. However, reports on the ultrasound imaging features and clinical conditions of NMCs are rare. The purpose of this study is to describe the ultrasound features and clinical analysis of NMCs to provide suggestions to identify the optimal management strategy. Methods From September 2020 to September 2021, 7 patients with a confirmed diagnosis of NMC who underwent ultrasound examination in our department were enrolled in our study. Physical examinations were performed to detect motor deficits, sensory deficits, neuropathic pain, limb undergrowth, muscular atrophy, cavus foot and bone dysplasia. Ultrasound imaging was performed and investigated both in affected nerves and neuromuscular choristomas associated desmoid-type fibromatosis (NMC-DTF). All patients had a definite history and regular follow-up. The clinical course, physical examinations, ultrasound features and pathologic results of NMC patients were analyzed. Results Seven patients with an average age of 7.0 ± 7.2 years (range: 2–22 years) were enrolled in our study. The affected nerves included the sciatic nerve (6 cases) and the brachial plexus (1 case). Six patients (85.7%) presented with limb undergrowth, 6 (85.7%) with muscular atrophy, and 5 (71.4%) with cavus foot deformity. Based on ultrasound findings, all the visibly affected nerve segments presented with hypoechoic and fusiform enlargement with intraneural skeletal muscle elements. Five patients (71.4%) had NMC-DTFs at the site of the affected nerve. All NMC-DTFs were shown as hypoechoic solid lesions adjacent to the nerve and were well circumscribed. In the subset of the surgery group, all 5 patients presented with progression to NMC-DTFs at the site of the NMCs. No fibromatosis was detected in the other two nonsurgical patients. Conclusions Understanding the typical ultrasound features and clinically associated conditions would support the early diagnosis of this rare disease. When a potential diagnosis is determined, an invasive procedure such as biopsy or resection might not be a good choice given the frequent occurrence of complications such as aggressive recurrence.

Toni Wendler, Melanie Edel, Robert Möbius et al.

Abstract Background Intraoperative proximal femoral fractures (IPFF) are relevant complications during total hip arthroplasty. Fixation using cerclage wires (CW) represents a minimally-invasive technique to address these fractures through the same surgical approach. The goal of treatment is to mobilise the patient as early as possible, which requires high primary stability. This study aimed to compare different cerclage wire configurations fixing IPFF with regard to biomechanical primary stability. Methods Standardised IPFF (type II, Modified Mallory Classification) were created in human fresh frozen femora and were fixed either by two or three CW (1.6 mm, stainless steel). All cadaveric specimens (n = 42) were randomised to different groups (quasi-static, dynamic) or subgroups (2 CW, 3 CW) stratified by bone mineral density determined by Dual Energy X-ray Absorptiometry. Using a biomechanical testing setup, quasi-static and dynamic cyclic failure tests were carried out. Cyclic loading started from 200 N to 500 N at 1 Hz with increasing peak load by 250 N every 100 cycles until failure occurred or maximum load (5250 N) reached. The change of fracture gap size was optically captured. Results No significant differences in failure load after quasi-static (p = 0.701) or dynamic cyclic loading (p = 0.132) were found between the experimental groups. In the quasi-static load testing, all constructs resisted 250% of the body weight (BW) of their corresponding body donor. In the dynamic cyclic load testing, all but one construct (treated by 3 CW) resisted 250% BW. Conclusions Based on this in vitro data, both two and three CW provided sufficient primary stability according to the predefined minimum failure load (250% BW) to resist. The authors recommend the treatment using two CW because it reduces the risk of vascular injury and shortens procedure time.

Aleksandra Bukiej, Winston Sequiera

Minh Huynh, Stéphanie Piazza

Schroeder Guido, Vivell Laura-Marie, Andresen Reimer et al.

Wen Hui Tan, Bich Ngoc Tran, Daria Larionova et al.

Goran Radunović, Zoran Veličković, Melanija Rašić et al.

Abstract Background The aim of the study was to assess gait pattern of patients diagnosed with fibromyalgia (FM) while performing demanding motor and/or cognitive dual tasks while walking. Further, idea was to explore possible correlations of dual task gait pattern alterations to patients’ functional status and presence or absence of clinical symptoms associated with FM. Methods Twenty-four female FM patients and 24 healthy female subjects performed a basic walking task, a dual motor, a dual mental (cognitive) and a combined, dual motor and cognitive task simultaneously. Quantitative spatial (stride length) and temporal (cycle time, swing time and double support time) gait parameters were measured using GAITRite walkway system and their variability was assessed. Patients underwent clinical examination including assessment of functional status, pain and fatigue level, psychiatric and cognitive manifestations. Results The motor, cognitive and combined dual tasks affect gait performance in FM patients. Difference in tasks between FM and healthy subjects was found as double support time prolongation. Comparison of tasks showing that cycle time in FM was longer than controls and stride length was shorter in patients for all conditions, while no changes were found in any of the gait parameters variability. Further, mental/cognitive dual tasks had a larger effect than motor tasks. Correlations were also found between depression and functional status of the patients and the gait parameters. Conclusions Gait is affected in FM patients while dual task walking. No changes in stride-to-stride variability point that patients preserve stability in complex walking situations. Analysis of gait may provide additional information for the FM identification based on presence of clinical features and cognitive status. Correlation of dual task gait alterations with occurrence of clinical symptoms and influence of cognitive changes on gait pattern could additionally define FM subgroups.

Daniel R. Lu, Andrew N. McDavid, Sarah Kongpachith et al.

Objective Rheumatoid arthritis ( RA ) is characterized by the activation of B cells that produce anti–citrullinated protein antibodies ( ACPA s) and rheumatoid factors ( RF s), but the mechanisms by which tolerance is broken in these B cells remain incompletely understood. We undertook this study to investigate whether ACPA + and RF + B cells break tolerance through distinct molecular mechanisms. Methods We developed antigen–tetramers to isolate ACPA + and RF + B cells and performed single‐cell RNA sequencing on 2,349 B cells from 6 RA patients and 1 healthy donor to analyze their immunoglobulin repertoires and transcriptional programs. Prominent immunoglobulins were expressed as monoclonal antibodies and tested for autoantigen reactivity. Results ACPA + and RF + B cells were enriched in the peripheral blood of RA patients relative to healthy controls. Characterization of patient‐derived monoclonal antibodies confirmed ACPA and RF targeting of tetramer‐specific B cells at both antigen‐inexperienced and affinity‐matured B cell stages. ACPA + B cells used more class‐switched isotypes and exhibited more somatic hypermutations relative to RF + B cells, and these differences were accompanied by down‐regulation of CD 72 and up‐regulation of genes that promote class‐switching and T cell–dependent responses. In contrast, RF + B cells expressed transcriptional programs that stimulate rapid memory reactivation through multiple innate immune pathways. Coexpression analysis revealed that ACPA + and RF + B cell–enriched genes belong to distinct transcriptional regulatory networks. Conclusion Our findings suggest that ACPA + and RF + B cells are imprinted with distinct transcriptional programs, which suggests that these autoantibodies associated with increased inflammation in RA arise from 2 different molecular mechanisms.

Blair A Jenkins, Natalia M Fontecilla, Catherine P Lu et al.

Touch sensation is initiated by mechanosensory neurons that innervate distinct skin structures; however, little is known about how these neurons are patterned during mammalian skin development. We explored the cellular basis of touch-receptor patterning in mouse touch domes, which contain mechanosensory Merkel cell-neurite complexes and abut primary hair follicles. At embryonic stage 16.5 (E16.5), touch domes emerge as patches of Merkel cells and keratinocytes clustered with a previously unsuspected population of Bmp4-expressing dermal cells. Epidermal Noggin overexpression at E14.5 disrupted touch-dome formation but not hair-follicle specification, demonstrating a temporally distinct requirement for BMP signaling in placode-derived structures. Surprisingly, two neuronal populations preferentially targeted touch domes during development but only one persisted in mature touch domes. Finally, Keratin-17-expressing keratinocytes but not Merkel cells were necessary to establish innervation patterns during development. These findings identify key cell types and signaling pathways required for targeting Merkel-cell afferents to discrete mechanosensory compartments.