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However, the involvement of M2 macrophages in mediating NP pathological angiogenesis and their underlying mechanisms remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Firstly, the expression of M2 macrophage (CD206) and microangiogenic (CD34) markers in human degenerated NP was observed by immunohistochemical staining, subsequently, a co-culture system of M2 macrophages and NP cells was established. IL-10 expression was silenced using siRNA to assess the pro-angiogenic effects of M2 macrophages in IDD via IL-10 and its downstream janus kinase (JAK) 2\/ signal transducer and activator of transcription (STAT) 3 pathway. AG490, a specific JAK2\/STAT3 inhibitor, was applied to determine whether IL-10 exerts its effects through this pathway and to evaluate its impact on angiogenesis and extracellular matrix (ECM) metabolism in NP pathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CD206 and CD34 were co-expressed in degenerated NP tissue. Degenerated NP cells secreted CCL17, CCL18, and CD206, exhibiting M2-like characteristics. Co-culture of M2 macrophages with degenerated NP cells led to IL-10 secretion to promote CD34 expression, and downregulated anabolic genes (type II collagen (COL2), aggrecan), and upregulated catabolic genes (matrix metalloproteinase (MMP)-3, MMP-7). JAK2 and STAT3 expression was significantly increased following co-culture. Activation of the JAK2\/STAT3 pathway enhanced vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (VEGFR), and CD34 expression and induced further downregulation of COL2 and aggrecan and upregulation of MMP-3 and MMP-7.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>M2 macrophage infiltration and pathological neovascularization are prominent in degenerated NP tissue. IL-10 secreted by M2 macrophages activates the JAK2\/STAT3 pathway to promote pathological microangiogenesis by up-regulate the expression of VEGF\/VEGFR. This process disrupts ECM and accelerates the progression of IDD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial number<\/jats:title>\n                    <jats:p>Not applicable.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13018-025-05962-2","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T22:47:00Z","timestamp":1748386020000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["M2 macrophages activate the IL-10\/JAK2\/STAT3 pathway to induce pathological microangiogenesis in the nucleus pulposus exacerbating intervertebral disc degeneration"],"prefix":"10.1186","volume":"20","author":[{"given":"Si-ping","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Mo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen-Yu","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Fei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,28]]},"reference":[{"issue":"10","key":"5962_CR1","doi-asserted-by":"publisher","first-page":"3148","DOI":"10.1007\/s11606-021-06732-6","volume":"36","author":"EJ Roseen","year":"2021","unstructured":"Roseen EJ, Rajendran I, Stein P, et al. 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