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OBJECTIVE The aim was to identify the source of cells within the center of the abnormal fibrocartilage tissue of the degenerative intervertebral disc after injury. DESIGN Cross-breeding of mice with an inducible type II promoter collagen construct (Col2CreER) to Rosa26-TdTomato mice has been shown to result in Cre-recombinase activity and Tomato expression in inner annulus fibrosus cells after tamoxifen injection. To investigate the role of the inner annulus fibrosus in the intervertebral disc injury response, tail intervertebral discs of Col2CreER/tdTomato mice were punctured with a needle and examined 1-4 wks after injury. N-cadherin was examined by immunostaining. RESULTS After the injury, the fibrocartilage in the degenerative intervertebral disc consisted of residual diseased nucleus pulposus cells and encroaching inner annulus fibrosus cells. The residual nucleus pulposus cells had lost their epithelial cell-like morphology and instead became oval shaped, with reduced adhesion to neighboring nucleus pulposus cells. This change in cellular morphology coincided with a loss of N-cadherin, which contributes to maintenance of healthy nucleus pulposus cell morphology. As expected, injured tail intervertebral discs showed reduced compressive properties as determined by biomechanical assessments. CONCLUSIONS The cellular composition of the degenerative intervertebral disc has been defined here, which is an important step in developing future treatments.

Cartilage is essential throughout vertebrate life. It starts developing in embryos when osteochondroprogenitor cells commit to chondrogenesis, activate a pancartilaginous program to form cartilaginous skeletal primordia, and also embrace a growth-plate program to drive skeletal growth or an articular program to build permanent joint cartilage. Various forms of cartilage malformation and degeneration diseases afflict humans, but underlying mechanisms are still incompletely understood and treatment options suboptimal. The transcription factor SOX9 is required for embryonic chondrogenesis, but its postnatal roles remain unclear, despite evidence that it is down-regulated in osteoarthritis and heterozygously inactivated in campomelic dysplasia, a severe skeletal dysplasia characterized postnatally by small stature and kyphoscoliosis. Using conditional knockout mice and high-throughput sequencing assays, we show here that SOX9 is required postnatally to prevent growth-plate closure and preosteoarthritic deterioration of articular cartilage. Its deficiency prompts growth-plate chondrocytes at all stages to swiftly reach a terminal/dedifferentiated stage marked by expression of chondrocyte-specific (Mgp) and progenitor-specific (Nt5e and Sox4) genes. Up-regulation of osteogenic genes (Runx2, Sp7, and Postn) and overt osteoblastogenesis quickly ensue. SOX9 deficiency does not perturb the articular program, except in load-bearing regions, where it also provokes chondrocyte-to-osteoblast conversion via a progenitor stage. Pathway analyses support roles for SOX9 in controlling TGFβ and BMP signaling activities during this cell lineage transition. Altogether, these findings deepen our current understanding of the cellular and molecular mechanisms that specifically ensure lifelong growth-plate and articular cartilage vigor by identifying osteogenic plasticity of growth-plate and articular chondrocytes and a SOX9-countered chondrocyte dedifferentiation/osteoblast redifferentiation process.

Meniscal tears are associated with a high risk of osteoarthritis but currently have no disease-modifying therapies. Using a Gli1 reporter line, we found that Gli1+ cells contribute to the development of meniscus horns from 2 weeks of age. In adult mice, Gli1+ cells resided at the superficial layer of meniscus and expressed known mesenchymal progenitor markers. In culture, meniscal Gli1+ cells possessed high progenitor activities under the control of Hh signal. Meniscus injury at the anterior horn induced a quick expansion of Gli1-lineage cells. Normally, meniscal tissue healed slowly, leading to cartilage degeneration. Ablation of Gli1+ cells further hindered this repair process. Strikingly, intra-articular injection of Gli1+ meniscal cells or an Hh agonist right after injury accelerated the bridging of the interrupted ends and attenuated signs of osteoarthritis. Taken together, our work identified a novel progenitor population in meniscus and proposes a new treatment for repairing injured meniscus and preventing osteoarthritis.

To investigate serum interleukin (IL)- 35 levels in patients with rheumatoid arthritis (RA) and to describe the association between serum IL-35 levels and clinical parameters: erythrocyte sedimentation rate (ESR), C reactive protein (CRP), global health on Visual Analog Scale, Disease Activity Score in 28 joints based on ESR (DAS28-ESR), rheumatoid factor (RF) and anticyclic citrullinated peptide antibodies (ACPAs). The study included 129 patients with RA and 83 healthy controls. Serum IL-35 levels were detected by ELISA. ESR and CRP were measured by the Westergren method and the immune transmission turbidity method, respectively. RF and ACPA were measured using immunoturbidimetric assays and chemiluminescence analysis, respectively. The results showed that serum IL-35 levels were elevated in patients with RA. Univariate and multivariate analyses showed that the high serum IL-35 levels were correlated with low ESR and DAS28-ESR. These suggested that IL-35, an important anti-inflammatory cytokine, may participate in the regulation of the pathogenesis of RA, especially with disease activity.

In studies of electron and proton radiotherapy, ultrahigh dose rates of FLASH radiotherapy appear to produce fewer toxicities than standard dose rates while maintaining local tumor control. FLASH-proton radiotherapy (F-PRT) brings the spatial advantages of PRT to FLASH dose rates (>40 Gy/second), making it important to understand if and how F-PRT spares normal tissues while providing antitumor efficacy that is equivalent to standard-proton radiotherapy (S-PRT). Here we studied PRT damage to skin and mesenchymal tissues of muscle and bone and found that F-PRT of the C57BL/6 murine hind leg produced fewer severe toxicities leading to death or requiring euthanasia than S-PRT of the same dose. RNA-seq analyses of murine skin and bone revealed pathways upregulated by S-PRT yet unaltered by F-PRT, such as apoptosis signaling and keratinocyte differentiation in skin, as well as osteoclast differentiation and chondrocyte development in bone. Corroborating these findings, F-PRT reduced skin injury, stem cell depletion, and inflammation, mitigated late effects including lymphedema, and decreased histopathologically detected myofiber atrophy, bone resorption, hair follicle atrophy, and epidermal hyperplasia. F-PRT was equipotent to S-PRT in control of two murine sarcoma models, including at an orthotopic intramuscular site, thereby establishing its relevance to mesenchymal cancers. Finally, S-PRT produced greater increases in TGFβ1 in murine skin and the skin of canines enrolled in a phase I study of F-PRT versus S-PRT. Collectively, these data provide novel insights into F-PRT-mediated tissue sparing and support its ongoing investigation in applications that would benefit from this sparing of skin and mesenchymal tissues. Significance: These findings will spur investigation of FLASH radiotherapy in sarcoma and additional cancers where mesenchymal tissues are at risk, including head and neck cancer, breast cancer, and pelvic malignancies.

Heterotopic ossification (HO) is a common, potentially debilitating pathology that is instigated by inflammation caused by tissue damage or other insults, which is followed by chondrogenesis, osteogenesis, and extraskeletal bone accumulation. Current remedies are not very effective and have side effects, including the risk of triggering additional HO. The TGF-β family member activin A is produced by activated macrophages and other inflammatory cells and stimulates the intracellular effectors SMAD2 and SMAD3 (SMAD2/3). Because HO starts with inflammation and because SMAD2/3 activation is chondrogenic, we tested whether activin A stimulated HO development. Using mouse models of acquired intramuscular and subdermal HO, we found that blockage of endogenous activin A by a systemically administered neutralizing antibody reduced HO development and bone accumulation. Single-cell RNA-seq analysis and developmental trajectories showed that the antibody treatment reduced the recruitment of Sox9+ skeletal progenitors, many of which also expressed the gene encoding activin A (Inhba), to HO sites. Gain-of-function assays showed that activin A enhanced the chondrogenic differentiation of progenitor cells through SMAD2/3 signaling, and inclusion of activin A in HO-inducing implants enhanced HO development in vivo. Together, our data reveal that activin A is a critical upstream signaling stimulator of acquired HO in mice and could represent an effective therapeutic target against forms of this pathology in patients.

Bone is maintained by coupled activities of bone-forming osteoblasts/osteocytes and bone-resorbing osteoclasts. Alterations in this relationship can lead to pathologic bone loss such as osteoporosis. It is well known that osteogenic cells support osteoclastogenesis via production of RANKL. Interestingly, our recently identified bone marrow mesenchymal cell population-marrow adipogenic lineage precursors (MALPs) that form a multidimensional cell network in bone-was computationally demonstrated to be the most interactive with monocyte-macrophage lineage cells through high and specific expression of several osteoclast regulatory factors, including RANKL. Using an adipocyte-specific Adipoq-Cre to label MALPs, we demonstrated that mice with RANKL deficiency in MALPs have a drastic increase in trabecular bone mass in long bones and vertebrae starting from 1 month of age, while their cortical bone appears normal. This phenotype was accompanied by diminished osteoclast number and attenuated bone formation at the trabecular bone surface. Reduced RANKL signaling in calvarial MALPs abolished osteolytic lesions after LPS injections. Furthermore, in ovariectomized mice, elevated bone resorption was partially attenuated by RANKL deficiency in MALPs. In summary, our studies identified MALPs as a critical player in controlling bone remodeling during normal bone metabolism and pathological bone loss in a RANKL-dependent fashion.

© 2021 The Authors. Osteoarthritis (OA) is a widespread joint disease for which there are no disease-modifying treatments. Previously, we found that mice with cartilage-specific epidermal growth factor receptor (EGFR) deficiency developed accelerated knee OA. To test whether the EGFR pathway can be targeted as a potential OA therapy, we constructed two cartilage-specific EGFR overactivation models in mice by overexpressing heparin binding EGF-like growth factor (HBEGF), an EGFR ligand. Compared to wild type, Col2-Cre HBEGF-overexpressing mice had persistently enlarged articular cartilage from adolescence, due to an expanded pool of chondroprogenitors with elevated proliferation ability, survival rate, and lubricant production. Adult Col2-Cre HBEGF-overexpressing mice and Aggrecan-CreER HBEGF-overexpressing mice were resistant to cartilage degeneration and other signs of OA after surgical destabilization of the medial meniscus (DMM). Treating mice with gefitinib, an EGFR inhibitor, abolished the protective action against OA in HBEGF-overexpressing mice. Polymeric micellar nanoparticles (NPs) conjugated with transforming growth factor-α (TGFα), a potent EGFR ligand, were stable and nontoxic and had long joint retention, high cartilage uptake, and penetration capabilities. Intra-articular delivery of TGFα-NPs effectively attenuated surgery-induced OA cartilage degeneration, subchondral bone plate sclerosis, and joint pain. Genetic or pharmacologic activation of EGFR revealed no obvious side effects in knee joints and major vital organs in mice. Together, our studies demonstrate the feasibility of using nanotechnology to target EGFR signaling for OA treatment.

Meniscal tears are associated with a high risk of osteoarthritis but currently have no disease-modifying therapies. Using Gli1-CreER tdTomato mice, we found that Gli1+ cells contribute to the development of meniscus horns from 2 weeks of age. In adult mice, Gli1+ cells resided at the superficial layer of meniscus and expressed known mesenchymal progenitor markers. In culture, meniscal Gli1+ cells possessed high progenitor activities under the control of Hh signal. Meniscus injury at the anterior horn induced a quick expansion of Gli1+ cells. Normally, the tissue healed slowly, leading to cartilage degeneration. Ablation of Gli1+ cells further hindered this repair process. Strikingly, intra-articular injection of Gli1+ meniscal cells or an Hh activator right after injury accelerated the bridging of the interrupted ends and attenuated signs of osteoarthritis. Taken together, our work identified a novel progenitor population in meniscus and proposes a new treatment for repairing injured meniscus and preventing osteoarthritis.

Bone is maintained by coupled activities of bone-forming osteoblasts/osteocytes and bone-resorbing osteoclasts and an alternation of this relationship can lead to pathologic bone loss such as in osteoporosis. It is well known that osteogenic cells support osteoclastogenesis via synthesizing RANKL. Interestingly, our recently identified bone marrow mesenchymal cell population—marrow adipogenic lineage precursors (MALPs) that form a multi-dimensional cell network in bone—was computationally demonstrated to be the most interactive with monocyte-macrophage lineage cells through highly and specifically expressing several osteoclast regulatory factors, including RANKL. Using an adipocyte-specific Adipoq-Cre to label MALPs, we demonstrated that mice with RANKL deficiency in MALPs have a drastic increase of trabecular bone mass in long bones and vertebrae starting from 1 month of age but that their cortical bone is normal. This phenotype was accompanied by diminished osteoclast number and attenuated bone formation at the trabecular bone surface. Reduced RANKL signaling in calvarial MALPs also abolished osteolytic lesions after lipopolysaccharide (LPS) injections. Furthermore, in ovariectomized mice, elevated bone resorption was partially attenuated by RANKL deficiency in MALPs. In summary, our studies identified MALPs as a critical player in controlling bone remodeling during normal bone metabolism and pathological bone loss in a RANKL-dependent fashion.

Our purpose is to study the roles of microRNA-338-5p (miR-338-5p) on the proliferation, invasion, and inflammatory response of fibroblast-like synoviocytes (SFs) in rheumatoid arthritis patients by regulating SPRY1. The target relationship between miR-338-5p and SPRY1 was validated through luciferase reporter system. The expression of miR-338-5p and SPRY1 in synovial tissues and synovial cells were detected using RT-PCR and western blot. The mimics and inhibitors of miR-338-5p were transfected into SFs. MTT, Transwell, and ELISA assays were used to analyze cell proliferation, invasiveness, and the secreted extracellular pro-inflammatory cytokines (such as IL-1a, IL-6, COX2) levels of SFs. MiR-338-5p was highly expressed in rheumatoid arthritis tissues and cells, and directly down-regulated the expression of SPRY1 in the SFs of rheumatoid arthritis patients. Cell proliferation, invasiveness and the expression level of pro-inflammatory cytokines in synovial cells increased after the transfection of miR-338-5p mimics, while the proliferation, invasion and expression level of pro-inflammatory cytokines decreased after the transfection of miR-338-5p inhibitors. In conclusion,miR-338-5p promoted the proliferation, invasion and inflammatory reaction in SFs of rheumatoid arthritis by directly down-regulating SPRY1 expression. J. Cell. Biochem. 118: 2295-2301, 2017. © 2017 Wiley Periodicals, Inc.

Objective. IL-35 was reported as a crucial anti-inflammatory cytokine and could efficiently regulate bone metabolism in murine collagen-induced arthritis model. However, the relationship between IL-35 and bone health in human rheumatoid arthritis (RA) has not been clarified. In this study, the aim was to explore the correlations between IL-35 and bone loss in postmenopausal women with RA. Methods. The study included 76 postmenopausal women with RA and 53 healthy postmenopausal women as healthy controls (HCs). Serum IL-35 levels were detected by enzyme-linked immunosorbent assay. Bone mineral density (BMD) at lumbar spine 1-4 and at total hip was measured using dual-energy X-ray absorptiometry. Alkaline phosphatase (ALP), β-isomerised carboxy-terminal cross-linking telopeptide of type I collagen (β-CTX), and 25-(OH) VitD3 were measured by turbidimetric inhibition immunoassay. Results. Serum IL-35 levels were increased compared with HCs, and it positively correlated with BMD and 25-(OH) VitD3 and negatively correlated with β-CTX in postmenopausal women with RA. Furthermore, serum IL-35 levels in the increased ALP group were higher than those in the normal ALP group. Conclusions. IL-35, an important anti-inflammatory cytokine, may participate in the pathogenesis of bone loss in postmenopausal women with RA.

Objective To investigate the effect of interleukin-35 (IL-35) on vascular endothelial growth factor (VEGF) and its receptors, Flt-1 and Flk-1, in a collagen-induced arthritis (CIA) mouse model of rheumatoid arthritis (RA). Methods We established a CIA mouse model and injected IL-35 intraperitoneally. The articular index (AI) was measured based on the amount of erythema, swelling, or joint rigidity and synovial histology was measured by hematoxylin and eosin staining (HE staining). The levels of VEGF, Flt-1, Flk-1, and von Willebrand factor (vWF) expression in CIA synovial tissue were determined by immunohistochemistry. The mRNA and protein expression levels of VEGF, Flt-1, Flk-1, TNF-α, and INF-γ were detected by reverse transcription PCR (RT-PCR) and western blots, respectively. Results The IL-35 treatment decreased the AI and the synovial histological scores of CIA mice. Immunohistochemistry results revealed that the IL-35 treatment downregulated VEGF, Flt-1, Flk-1, and vWF expression in the CIA mice. RT-PCR results showed that the IL-35-treated mice had lower levels of VEGF, Flt-1, Flk-1, and TNF-α mRNA expression than those of the PBS-treated mice. While there was no significant difference in the level of INF-γ mRNA expression between IL-35-treated and PBS-treated mice. Western blot results showed that the IL-35 treatment downregulated the levels of VEGF, Flt-1, Flk-1, and TNF-α in CIA mice, but the level of INF-γ was not significantly affected. Conclusion These findings show that IL-35 may represent a novel therapeutic agent for RA, and the probable mechanisms may rely on inhibiting VEGF and its receptors Flt-1 and Flk-1.

Atrophic nonunion represents an extremely challenging clinical dilemma for both physicians and fracture patients alike, but its underlying mechanisms are still largely unknown. Here, we established a mouse model that recapitulates clinical atrophic nonunion through the administration of focal radiation to the long bone midshaft 2 weeks before a closed, semistabilized, transverse fracture. Strikingly, fractures in previously irradiated bone showed no bony bridging with a 100% nonunion rate. Radiation triggered distinct repair responses, separated by the fracture line: a less robust callus formation at the proximal side (close to the knee) and bony atrophy at the distal side (close to the ankle) characterized by sustained fibrotic cells and type I collagen-rich matrix. These fibrotic cells, similar to human nonunion samples, lacked osteogenic and chondrogenic differentiation and exhibited impaired blood vessel infiltration. Mechanistically, focal radiation reduced the numbers of periosteal mesenchymal progenitors and blood vessels and blunted injury-induced proliferation of mesenchymal progenitors shortly after fracture, with greater damage particularly at the distal side. In culture, radiation drastically suppressed proliferation of periosteal mesenchymal progenitors. Radiation did not affect hypoxia-induced periosteal cell chondrogenesis but greatly reduced osteogenic differentiation. Lineage tracing using multiple reporter mouse models revealed that mesenchymal progenitors within the bone marrow or along the periosteal bone surface did not contribute to nonunion fibrosis. Therefore, we conclude that atrophic nonunion fractures are caused by severe damage to the periosteal mesenchymal progenitors and are accompanied by an extraskeletal, fibro-cellular response. In addition, we present this radiation-induced periosteal damage model as a new, clinically relevant tool to study the biologic basis of therapies for atrophic nonunion. © 2018 American Society for Bone and Mineral Research.

Background Interactions of inflammatory cells with pancreatic cancer cells play crucial roles in pancreatic cancer, however the dynamic changes of inflammatory cell populations in pancreatic cancerogensis and after chemotherapy have not been well eclucidated. The combinational use of aspirin and atrovastatin (Lipitor) have been widely prescribled for cardio-cerebral vascular diseases mainly by regulation of inflammations, and they have been also reported to have plausible anti-tumor effects, however their potential roles in pancreatic cancerogenesis and chemotherapeutic effects have been seldom investigated. We scanned the dynamic changes of pan-inflammatory cell populations in pancreatic cancerogensis and after chemotherapy and found the potential target cell populations. Then we tested the roles of aspirin and Lipitor to regulate these inflammatory cell populations and their effects on pancreatic cancerogenesis and chemotherapeutic effects. Methods Cancerogen, dimethylbenzanthracene (DMBA), was used to induce pancreatic cancerogenesis and subcatunous implantation of syngenic murine Panc02 pancreatic cancer cells was adopted as well. Gemcitabine was used for chemotherapy. The peripheral blood, pancreatic lesions and tumor samples were harvested and analyzed to search for the potential target cell populations. The roles of aspirin and Lipitor to regulate these cell populations and their potential effects on pancreatic cancerogenesis and chemotherapeutic efficacy were investigated both in vitro and in vivo. Results We found progressive accumulations of myeloid-derived suppressor cells (MDSC) and M2-polarzied tumor associated macrophages(M2) in pancreatic lesions accompanied with dynamic reducations of cytotoxic T cells(CTL) and helper T cells(Th) in the progression of pancreatic cancerogenesis. After gemcitabine treatment, the MDSC significantly reduced, however M2 soared up unexpectedly. Aspirin could significantly inhibit the MDSC and M2 to prevent pancreatic cancerogenesis and improve chemotherapeutic effects of gemcitabine, however Lipitor did not significantly affect MDSC, instead it could promote M2 to attenuate the postive effects of aspirin and gemcitabine. Conclusions MDSC and M2 accumulate in progression of pancreatic cancerogenesis and gemcitabine can induce M2. Aspirin could prevent pancreatic cancerogenesis and improve efficacy of gemcitabine partially by inhibiting MDSC and M2, however when used in combination, Lipitor could weaken the efficacy of aspirin and gemcitabine partially by promoting M2. Electronic supplementary material The online version of this article (doi:10.1186/s13046-016-0304-4) contains supplementary material, which is available to authorized users.

Glucose-regulated protein 78 (GRP78) is a member of the heat-shock protein 70 family. We evaluated the expression of GRP78 using tissue microarray-based immunohistochemistry in tumor tissues and adjacent nontumor tissues from 180 pancreatic ductal adenocarcinoma (PDAC) patients. The associations between the expression levels of GRP78, clinicopathological factors and overall survival were evaluated. The results showed that the expression of GRP78 was significantly higher in PDAC cells than in normal pancreatic duct cells within adjacent nontumor tissues (p in vitro study, the regulation of GRP78 in the PDAC cell lines affected the proliferation, migration and invasion of PDAC cells through the regulation of CyclinD1, cyclin-dependent kinase (CDK) 4, CDK6, phospho-signal transducer, activator of transcription 3 (p-STAT3), janus kinase 2 (JAK2), ras homolog gene family member A (RhoA), Rho-associated kinase 1 (ROCK1) and sterile alpha motif domain containing protein 4 (Smad4). The present data suggest that GRP78 plays a crucial role in the proliferation, migration and invasion of pancreatic cancer cells and may be a suitable prognostic marker in PDAC.

Objective To determine whether interleukin (IL)-33 and soluble ST2 (sST2) are associated with primary Sjogren’s Syndrome (pSS). Methods Serum levels of IL-33 and sST2 in 110 pSS patients and 78 healthy controls were measured by enzyme-linked immunosorbent assay (ELISA). Immunoglobulins, rheumatoid factors (RF), antinuclear antibody (ANA), anti-SSA/RO-52 antibody, anti-SSB antibody and erythrocyte sedimentation rate (ESR) were measured by standard laboratory techniques. Interstitial lung disease (ILD) was identified on high-resolution computed tomography (HRCT). Disease activity in pSS was scored with the European League Against Rheumatism Sjogren’s Syndrome Disease Activity Index (ESSDAI). Results Serum levels of IL-33 and sST2 were significantly elevated in pSS patients, especially in patients with ILD. There was significant positive correlation between IL-33 and RF, anti-SSB antibody. Conclusion IL-33/sST2 may be involved in the pathogenesis of pSS and partly contribute to the ILD in pSS patients.

Introduction Interleukin 27 (IL-27), belonging to the IL-12 family, exerts a critical role in immune regulation of infection, autoimmunity, and tumor. In this study, we aimed to investigate the roles of IL-27 and vascular endothelial growth factor (VEGF) in breast cancer. Methods The serum levels of IL-27 and VEGF in 150 patients with breast cancer and 90 control subjects were measured by an enzyme-linked immunosorbent assay. Estrogen receptor, progesterone receptor, and human epithelial growth factor receptor 2 were measured by immunohistochemistry. Clinical stage, tumor size, lymph node metastasis, grade, and histological type were also recorded. Results The serum levels of IL-27 and VEGF were significantly greater in breast cancer patients than in the control group. In addition, there was a significant correlation between IL-27 and VEGF, and serum IL-27 and VEGF levels were associated with the clinical stage of breast cancer. Moreover, the serum levels of IL-27 were especially elevated in breast cancer patients who were estrogen receptor–positive and progesterone receptor–positive. Furthermore, the serum levels of IL-27 and VEGF decreased after patients with breast cancer had modified radical mastectomy. Conclusion Interleukin 27 may be a new prognostic biomarker of breast cancer and a promising target to limit both angiogenesis and tumor growth.

Background ST2, a member of the interleukin (IL)-1receptor family, regulates Th1/Th2 immune responses in autoimmune and inflammatory conditions. However, the role of ST2 signaling in tumor growth and metastasis of breast cancers has not been investigated. This study investigated the possible role of soluble ST2 (sST2) in breast cancer. Methods The serum levels of IL-33, sST2, and vascular endothelial growth factor (VEGF) in 150 breast cancer patients and 90 healthy women were measured by enzyme-linked immunosorbent assay. Estrogen receptor(ER), progesterone receptor, human epithelial receptor (HER)-2, and cell cycle regulated protein Ki-67 were measured. Clinical stage, tumor size, lymph node metastasis, and histological type were also recorded. Results The serum levels of sST2, IL-33, and VEGF were significantly higher in breast cancer patients than in the control group (P P r = 0.375, P r = 0.164, P = 0.045). Serum levels of sST2, IL-33, and VEGF decreased after modified radical mastectomy in ER-positive breast cancers. Serum levels of IL-33, sST2, and VEGF and clinicopathological factors were not significantly correlated with disease-free survival and overall survival of ER-positive breast cancer women during follow-up. Conclusion Serum sST2 levels in ER-positive breast cancer patients are significantly associated with factors that indicate poor prognosis.