ArticleOrthopaedic surgery2023
ASPN Synergizes with HAPLN1 to Inhibit the Osteogenic Differentiation of Bone Marrow Mesenchymal Stromal Cells and Extracellular Matrix Mineralization of Osteoblasts.
Article in Orthopaedic surgery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 9 citations in OpenAlex.
- PDLSC-CM targets HAPLN1 in macrophages to reduce root resorption in delayed replanted teeth.Stem cell research & therapy · 2026Article
- Dynamic profiling of BMSC-dECM reveals accumulation of core matrisome proteins suppresses osteogenic differentiation and bone regeneration.Journal of advanced research · 2026Article
- Association between osteoporosis and rotator cuff tears: evidence from causal inference and colocalization analyses.Bone research · 2025Article
- Evolutionary balance between genomic conservation and coral reef adaptation in the yellow boxfish (Zoological research · 2025Article
- Transcription factor SMAD5 upregulates ALG5 to alleviate osteoporosis development by inducing osteogenic differentiation.Journal of orthopaedics · 2025Article
- The study on bone marrow mesenchymal stem cell-derived extracellular matrix promoting the repair of damaged chondrocytes by regulating the Notch1/RBPJ pathway.Cytotechnology · 2025Article
- BRD4 facilitates osteogenic differentiation of human bone marrow mesenchymal stem cells through WNT4/NF-κB pathway.Journal of orthopaedic surgery and research · 2023Article
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5 authors at 1 institution in 1 country.
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Abstract
objectiveBone marrow mesenchymal stromal cells (BMSCs) are major sources of osteogenic precursor cells in bone remodeling, which directly participate in osteoporosis (OP) progression. However, the involved specific mechanisms of BMSCs in OP warrant mass investigations. Initially, our bioinformatics analysis uncovered the prominent up-regulation of Asporin (ASPN) and proteoglycan link protein 1 (HAPLN1) in osteoblasts (OBs) of OP patients and their possible protein interaction. Hence, this study aimed to explore the effects of ASPN and HAPLN1 on osteogenic differentiation of BMSCs, extracellular matrix (ECM) mineralization of OBs, and osteoclastogenesis, hoping to offer research basis for OP treatment.
methodsGSE156508 dataset was used for analysis and screening to acquire the differentially expressed genes in OBs of OP patients, followed by the predicative analysis via STRING. OP mouse models were induced by ovariectomy (OVX), and ASPN and HAPLN1 expression was determined. BMSCs and bone marrow macrophages (BMMs) were isolated from OVX mice and induced for osteogenic differentiation and osteoclastogenesis, respectively. After knockdown experiments, we assessed adipogenic differentiation and osteogenic differentiation in BMSCs. Osteogenic (OPN, OCN, and COL1A1) and osteoclast (Nfatc1 and c-Fos) marker protein expression was determined. The binding of ASPN to HAPLN1 was analyzed.
resultsHigh expression of ASPN and HAPLN1 and their protein interaction were observed in OBs of OP patients via bioinformatics and in bone tissues of OVX mice. ASPN interacted with HAPLN1 in BMSCs of OVX mice. ASPN/HAPLN1 knockdown increased ALP, OPN, OCN, and COL1A1 protein expression and ECM mineralization in BMSCs while decreasing Nfatc1 and c-Fos expression in BMMs. These effects were aggravated by the simultaneous knockdown of ASPN and HAPLN1.
conclusionOur results indicate that ASPN synergises with HAPLN1 to suppress the osteogenic differentiation of BMSCs and ECM mineralization of OBs and promote the osteoclastogenesis in OP.
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