{"doi":"10.3389/fendo.2023.1331690","title":"Editorial: Fish as model organism for skeletal diseases","abstract":"Fish provide new insights into mechanisms of rare and common bone diseases.Osteogenesis imperfecta (OI), also known as brittle bone disease, is a rare disease clinically characterised by short stature, skeletal deformities, low bone mass and bone fragility. In most cases, it is caused by autosomal mutations in collagen type I. Zebrafish chihuahua (chi/-) mutants carry a heterozygous mutation in col1a1a and have long been used as model for OI. Although chihuahua represents a very well characterised model, in which rib fractures have been described, Cotti S et al. for the first-time report compression vertebral fractures associated with chi/-. Importantly, Cotti S et al. tested whether low dietary phosphorus intake mitigates the skeletal phenotypes associated with this model, partially restoring bone shape variation of the vertebral bodies and osteoid layer of endplates. Their research suggests that reduced dietary phosphorus intake has therapeutic potential to improve bone matrix and alleviate the severe bone phenotypes of OI.A recessive form of OI, classified as type XIV, is caused by mutations in TMEM38B, which encodes the trimeric intracellular cation channel Tric-b. Tonelli F et al. report new insights into TMEM38B function. They analysed spatiotemporal expression of tmem38a and tmem38b in zebrafish, and generated a zebrafish tmem38b loss-offunction mutant that developed a mild bone phenotype. Interestingly, collagen type I analyses revealed enlarged endoplasmic reticulum (ER) cisternae in tmem38b mutants. To investigate bone formation and remodelling, they performed TRAP staining after fin amputation, and showed differential staining in mutants, pointing to abnormal osteoclast activity. Abnormal actinotrichia formation in mutants after fin amputation supported a role for tmem38b in osteoclast activity.Mutations in COMP (cartilage oligomeric matrix protein) lead to chondrodysplasias. Forte-Gomez HF et al. revealed that comp is expressed in myosepta and notochord but unexpectedly not in cartilage of larval zebrafish. When they targeted comp using CRISPR/Cas9, irregular staining for Comp protein was detected in myosepta. Electron microscopy beautifully revealed disorganised extracellular matrix in mutants, indicating that Comp plays a role in matrix assembly, similar to what had been proposed for a subgroup of human chondrodysplasia patients. This work thus depicts the suitability of zebrafish myosepta to study extracellular matrix organisation associated with bone diseases.Collagen II is the most abundant collagen in cartilage, however, there are many questions regarding its secretory pathway in vivo. Ritter et al. generated loss-offunction mutants for rgp1. Prior to this study, the role of Rgp1 in protein trafficking had been examined in vitro and in yeast, however its role in vivo was unknown. Using multiple approaches including in vivo imaging of vesicular trafficking, electron microscopy, and overexpression, Ritter et al. found evidence for a Rgp1-regulated Rab6a-Rab8a pathway that directs secretion of collagen II. This study demonstrates how the favourable genetic and imaging attributes of zebrafish enable laboratories to pursue in vivo studies of collagen trafficking that may otherwise be considered too challenging or scientifically risky.Other than the above-mentioned rare bone diseases, osteoporosis affects millions of people worldwide. It is characterised by impaired bone microarchitecture, commonly associated with reduced bone mineral density (BMD), and increased fracture risk. LRP5, a co-receptor of the canonical Wnt pathway, has been associated with BMD through genome-wide association studies (GWASs). Diverse mutations in LRP5 are causative of osteoporosis-pseudoglioma syndrome, high-bone mass, and craniofacial malformations. Khrystoforova I et al. showed that zebrafish lrp5 mutants recapitulated a loss-of-function mutation phenotype found in humans. Transcriptomic profiling of mutants surprisingly suggested the ","journal":"Frontiers in Endocrinology","year":2023,"id":395384,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9472,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":313949,"name":"Ronald Y. Kwon","orcid":"0000-0001-9760-3761","position":1,"is_corresponding":false},{"id":430915,"name":"Christoph Winkler","orcid":"0000-0003-4688-6241","position":2,"is_corresponding":false},{"id":915673,"name":"Érika Kague","orcid":"0000-0002-0266-9424","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:19:22.857556Z","pmid":"38053724","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}