Growth factor profile in calcified cartilage from the metaphysis of a calf costochondral junction, the site of initial bone formation.

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In the present study, the growth factors were isolated from non-calcified and calcified cartilage of costochondral junctions. Cartilage dissected from the ribs of 6-20-week-old calves was purchased from a local butcher within 24 h of the death of the animal. The isolation involved hyaluronidase digestion, guanidinium hydrochloride (GuHCl) extraction, HCl decalcification and GuHCl extraction of the decalcified matrix. Growth factors were purified by heparin chromatography and their quantities were estimated using ELISA. Decalcified cartilage was also used for protein sequence analysis (data are available via ProteomeXchange; ID, PXD021781). Bone morphogenetic protein-7 (BMP-7), growth/differentiation factor-5 (GDF-5) and NEL-like protein-1 (NELL-1), all known growth factors that stimulate bone formation, quantitatively accounted for the majority of the material obtained in all steps of isolation. Thus, cartilage serves as a store for growth factors. During initial bone formation septoclasts release osteoclastogenesis-stimulating factors deposited in non-calcified cartilage. Osteoclasts dissolve calcified cartilage and transport the released factors required for the stimulation of osteoprogenitor cells to deposit osteoid. High concentrations of BMP-7, GDF-5 and NELL-1 at the site of initial bone formation may suggest that their synergistic action favours osteogenesis.", "claims": [{"id": "claim-data-access", "statement": "The datasets used and/or analysed during the present study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33884197", "locator": "sections[16] \"Availability of data and materials\" paragraph 2", "quote": "The datasets used and/or analysed during the present study are available from the corresponding author on reasonable request."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:33884197"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": [], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33884197", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3892/br.2021.1430", "sha256": "sha256:d7e8df7a59ac0ef1d597c1c9e5d26b75589c5dc679b82b27ebb7201b7b496657", "bytes": 54055, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3892/br.2021.1430", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8056382", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "asset:table:pmid:33884197:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:9a38495379487bb07d33f69ff8c93ccc969f372f081724a5555acade08f58ec0", "bytes": 982, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#tI-br-0-0-01430", "version": null, "note": "Concentration of growth factors in different fractions of calcified cartilage from calf costochondral junctionsa.", "structure": {"pmcid": "PMC8056382", "section_index": 12, "section_title": "Results", "row_count": 9, "column_count": 10}, "table": {"label": "Table I", "caption": "Concentration of growth factors in different fractions of calcified cartilage from calf costochondral junctionsa.", "rows": [["Fractions", "BMP-2", "BMP-3", "BMP-4", "BMP-7", "VEGF", "bFGF", "TGF-β1", "NELL-1", "GDF-5"], ["Fraction 1, Hyaluronidase digestion", "38", "6", "40", "236", "70", "12", "0", "587", "226"], ["", "52", "9", "32", "266", "56", "21.5", "0", "572", "347"], ["Fraction 2, GuHCl extraction after", "18", "8", "30", "133", "111", "16", "14", "612", "239"], ["hyaluronidase digestion", "37", "5", "68", "148", "51", "20", "32", "587", "285"], ["Fraction 3, HCl decalcification", "38", "4", "15", "253", "78", "15", "0", "550", "161"], ["after GuHCl extraction", "10", "5", "90", "276", "37", "15", "23", "387", "207"], ["Fraction 4, GuHCl extraction", "18", "8", "54", "533", "32", "12.5", "16", "650", "240"], ["after HCl decalcification", "19", "3", "87", "520", "15.7", "20.5", "23", "436", "140"]], "row_count": 9, "column_count": 10, "numeric_cells": 83, "header_rows": 1, "locator": "section[12]/table-wrap[1]#tI-br-0-0-01430"}}, {"id": "asset:table:pmid:33884197:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:f8cd15d88e17865c218ed37a90dcd0b9539cec1d3db906d07d26e91603591dd2", "bytes": 540, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[2]#tII-br-0-0-01430", "version": null, "note": "Growth factors found by sequence analysis of proteins released during decalcification in 0.6 N HCl, and in the decalcified material.", "structure": {"pmcid": "PMC8056382", "section_index": 12, "section_title": "Results", "row_count": 5, "column_count": 2}, "table": {"label": "Table II", "caption": "Growth factors found by sequence analysis of proteins released during decalcification in 0.6 N HCl, and in the decalcified material.", "rows": [["Factors", "Mascot score (number of matching peptides)"], ["Mesencephalic astrocyte-derived neurotropic", "966(7)"], ["Connective tissue growth factor", "739(8)"], ["Osteoclast stimulating factor", "243(4)"], ["Hepatoma-derived growth factor", "122(3)"]], "row_count": 5, "column_count": 2, "numeric_cells": 4, "header_rows": 1, "locator": "section[12]/table-wrap[2]#tII-br-0-0-01430"}}, {"id": "asset:table:pmid:33884197:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:1ffd5b714f0ea9b601b037aaad7e1e10b041009987b839db83937def3862d5af", "bytes": 2206, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#tIII-br-0-0-01430", "version": null, "note": "Growth factors that were present or absent, based on ELISA, in the rib costochondral junctions, and their role in endochondral ossification.", "structure": {"pmcid": "PMC8056382", "section_index": 13, "section_title": "Discussion", "row_count": 17, "column_count": 4}, "table": {"label": "Table III", "caption": "Growth factors that were present or absent, based on ELISA, in the rib costochondral junctions, and their role in endochondral ossification.", "rows": [["Growth factors", "Functions", "Concentration in calf costochondral junctions, pg/300 mg dry cartilagea", "Refs."], ["BMP-1", "Metalloprotease, cleaves procollagen, participates in bone repair.", "Not detected", "(17)"], ["BMP-2", "Induces endochondral bone formation", "115", "(47,19,48)"], ["BMP-4", "following in vivo implantation;", "208", ""], ["BMP-7", "participates in bone mineralization. Differences in dose and time needed for reactions. Facilitates both chondrogenic and osteogenic differentiation of mesenchymal stem cells.", "1,182.50", ""], ["BMP-3", "Induces endochondral bone formation following in vivo implantation, a negative modulator of bone formation, and an antagonist of BMP-2 signaling.", "23.5", "(19,48,50)"], ["BMP-5", "Induces endochondral bone formation following in vivo implantation, and participates in bone mineralization.", "Not detected", "(19,47)"], ["BMP-6", "Induces endochondral bone formation following in vivo implantation, and participates in bone mineralization.", "Not detected", "(19,47)"], ["TGF-β1", "Regulates replication and differentiation of cartilage and bone forming cells.", "27", "(60)"], ["bFGF", "Stimulates bone formation.", "16.75", "(76,77)"], ["IGF-1", "Functions in coupling bone resorption and formation.", "Not detected", "(75)"], ["VEGF", "Stimulates angiogenesis and endochondral bone formation.", "255.5", "(22)"], ["GDF-5", "Closely related to BMP-5,6,7. 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