{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPRELP, a collagen‐ and glycosaminoglycan‐binding protein highly expressed in cartilage and developing bone, plays a critical role in skeletal homeostasis by regulating bone cell function. In osteoclast precursors, PRELP is internalized via a chondroitin sulfate‐ and annexin II‐dependent mechanism and subsequently translocates to the nucleus, where it interacts with NF‑κB (p65) to inhibit its DNA binding and transcriptional activity. This, in turn, leads to reduced osteoclast-specific gene expression and diminished osteoclastogenesis, a feature further supported by detailed expression studies in cartilage during development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, PRELP positively influences osteoblast differentiation. Its increased expression during osteogenic induction enhances alkaline phosphatase activity, mineralization, and the expression of critical osteogenic markers such as Runx2. The underlying mechanism involves modulation of the β‑catenin/connexin43 signaling pathway, further confirming its role in promoting bone formation and remodeling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond the skeletal system, PRELP exerts beneficial effects in other tissues. In the context of age‑related macular degeneration (AMD), PRELP dampens complement-mediated damage by reducing membrane attack complex (MAC) accumulation, thereby protecting against choroidal neovascularization. In parallel, increased PRELP expression in fibrotic myocardium and liver tissues—where it is prominently expressed by chondrocyte-like myofibroblasts—stimulates collagen production, contributing to tissue fibrosis and adverse ventricular remodeling. These observations underscore PRELP’s multifunctional role in tissue homeostasis and its potential as a therapeutic target in both ocular and cardiovascular diseases."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "J Grover, P J Roughley "}, {"type": "b", "children": [{"type": "t", "text": "Characterization and expression of murine PRELP."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Matrix Biol (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0945-053x(01)00165-2"}], "href": "https://doi.org/10.1016/s0945-053x(01"}, {"type": "t", "text": "00165-2) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11731272"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11731272"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Nadia Rucci, Anna Rufo, Marina Alamanou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The glycosaminoglycan-binding domain of PRELP acts as a cell type-specific NF-kappaB inhibitor that impairs osteoclastogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200906014"}], "href": "https://doi.org/10.1083/jcb.200906014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19951916"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19951916"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Haiying Li, Yazhou Cui, Jing Luan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PRELP (proline/arginine-rich end leucine-rich repeat protein) promotes osteoblastic differentiation of preosteoblastic MC3T3-E1 cells by regulating the β-catenin pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2016.01.106"}], "href": "https://doi.org/10.1016/j.bbrc.2016.01.106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26809092"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26809092"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "M T Birke, E Lipo, M Adhi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AAV-mediated expression of human PRELP inhibits complement activation, choroidal neovascularization and deposition of membrane attack complex in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene Ther (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/gt.2014.24"}], "href": "https://doi.org/10.1038/gt.2014.24"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24670995"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24670995"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yu Zhang, Chunli Fu, Shaohua Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PRELP promotes myocardial fibrosis and ventricular remodelling after acute myocardial infarction by the wnt/β-catenin signalling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cardiovasc J Afr (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.5830/CVJA-2022-001"}], "href": "https://doi.org/10.5830/CVJA-2022-001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35788244"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35788244"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yuto Yamauchi, Hiroki Mieno, Haruna Suetsugu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Elevated PRELP expression in heart and liver fibrosis promotes collagen production."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2024.150785"}], "href": "https://doi.org/10.1016/j.bbrc.2024.150785"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "39369540"}], "href": "https://pubmed.ncbi.nlm.nih.gov/39369540"}]}]}]}