{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:14:36Z","timestamp":1789992876241,"version":"4.0.1"},"reference-count":167,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2023,12,5]],"date-time":"2023-12-05T00:00:00Z","timestamp":1701734400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["32172929"],"award-info":[{"award-number":["32172929"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Precise coupling of two fundamental mechanisms, chondrogenesis and osteogenesis via angiogenesis, plays a crucial role during rapid proliferation of growth plates, and alteration in their balance might lead to pathogenic conditions. Tibial dyschondroplasia (TD) is characterized by an avascular, non-mineralized, jade-white \u201ccartilaginous wedge\u201d with impaired endochondral ossification and chondrocyte proliferation at the proximal end of a tibial bone in rapidly growing poultry birds. Developing vascular structures are dynamic with cartilage growth and are regulated through homeostatic balance among pro and anti-angiogenic proteins and cytokines. Pro-angiogenic factors involves a wide spectrum of multifactorial mitogens, such as vascular endothelial growth factors (VEGF), platelet-derived growth factors (PDGF), basic fibroblast growth factor (bFGF), placental growth factors, transforming growth factor-\u03b2 (TGF-\u03b2), and TNF-\u03b1. Considering their regulatory role via the sonic hedgehog, notch-gridlock, and ephrin-B2\/EphB4 pathways and inhibition through anti-angiogenic proteins like angiostatin, endostatin, decoy receptors, vasoinhibin, thrombospondin, PEX, and troponin, their possible role in persisting inflammatory conditions like TD was studied in the current literature review. Balanced apoptosis and angiogenesis are vital for physiological bone growth. Any homeostatic imbalance among apoptotic, angiogenetic, pro-angiogenic, or anti-angiogenic proteins ultimately leads to pathological bone conditions like TD and osteoarthritis. The current review might substantiate solid grounds for developing innovative therapeutics for diseases governed by the disproportion of angiogenesis and anti-angiogenesis proteins.<\/jats:p>","DOI":"10.3390\/ani13243750","type":"journal-article","created":{"date-parts":[[2023,12,5]],"date-time":"2023-12-05T08:09:17Z","timestamp":1701763757000},"page":"3750","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Homeostatic Regulation of Pro-Angiogenic and Anti-Angiogenic Proteins via Hedgehog, Notch Grid, and Ephrin Signaling in Tibial Dyschondroplasia"],"prefix":"10.3390","volume":"13","author":[{"given":"Shah","family":"Nawaz","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9512-5230","authenticated-orcid":false,"given":"Muhammad Fakhar-e-Alam","family":"Kulyar","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Mo","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wangyuan","family":"Yao","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mudassar","family":"Iqbal","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Faculty of Veterinary and Animal Sciences, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6065-6648","authenticated-orcid":false,"given":"Jiakui","family":"Li","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18472","DOI":"10.1021\/acsami.0c22671","article-title":"Umbilical Mesenchymal Stem Cell-Derived Exosome-Encapsulated Hydrogels Accelerate Bone Repair by Enhancing Angiogenesis","volume":"13","author":"Zhang","year":"2021","journal-title":"ACS Appl. 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