Study on the Mechanism of PDGF-BB in the Pathological Process of Osteoarthritis

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Osteoarthritis, as a common degenerative joint disease, is characterized by abnormal angiogenesis of subchondral bone and vascular invasion into avascular joint cartilage tissue in its early stages. This process not only accelerates joint cartilage degeneration, but also leads to joint pain caused by nerve growth.

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Osteoarthritis, as a common degenerative joint disease, is characterized by abnormal angiogenesis in subchondral bone and vascular invasion into avascular articular cartilage in its early pathological stages. This process not only accelerates articular cartilage degeneration but also causes joint pain accompanied by nerve ingrowth. However, the key molecular mechanism initiating pathological angiogenesis in subchondral bone has long been unclear. Recent studies have found that platelet-derived growth factor-BB (PDGF-BB) secreted by preosteoclasts plays a core driving role in the pathogenesis of osteoarthritis, providing an important basis for understanding the early mechanisms of the disease and developing new therapeutic targets.

1. Characteristics of Subchondral Bone Angiogenesis in Early Osteoarthritis

In animal model studies of osteoarthritis, using destabilization of the medial meniscus (DMM) surgery to establish an osteoarthritis model, it was found that significant abnormal angiogenesis in subchondral bone appeared before articular cartilage degeneration occurred. Three-dimensional μCT imaging analysis showed that model mice exhibited increased bone volume/tissue volume ratio, thickened subchondral bone plate, and changed trabecular parameters in the early postoperative period, indicating that abnormal angiogenesis is an early event in the development of osteoarthritis, preceding obvious degeneration of cartilage tissue.

These pathological changes are highly consistent with the clinical diagnostic characteristics of osteoarthritis, suggesting that subchondral bone angiogenesis may be an important initiating factor in disease progression. Evaluation using the Osteoarthritis Research Society International (OARSI) scoring system showed that as the degree of subchondral bone angiogenesis increased, the articular cartilage degeneration score increased synchronously, confirming a close association between abnormal angiogenesis and cartilage damage, providing a pathological basis for exploring early intervention targets.

2. Abnormal Secretion of PDGF-BB and Activation of Angiogenic Signals

Molecular mechanism studies on osteoarthritis model mice revealed that the expression level of PDGF-BB in subchondral bone increased significantly in the early stage of the disease. Immunofluorescence detection found that PDGF-BB-positive cells were mainly localized in mononuclear preosteoclasts in subchondral bone, and their number in model mice was nearly twice that in normal mice. Quantitative ELISA analysis further confirmed that the concentrations of PDGF-BB protein in subchondral bone marrow and serum of model mice were significantly increased and continued to rise with disease progression, suggesting that PDGF-BB may participate in the disease process as a systemic signal.

PDGF-BB exerts its biological effects by activating its receptor PDGFR-β. Triple immunofluorescence staining showed that the expression level of phosphorylated PDGFR-β (p-PDGFR-β) in vascular pericytes of subchondral bone in model mice was significantly upregulated, and there was a spatial colocalization relationship with CD31hiEmcnhi-positive vascular structures. This result indicates that PDGF-BB excessively secreted by preosteoclasts can specifically activate the PDGFR-β signaling pathway in vascular pericytes, thereby promoting the formation of new blood vessels in subchondral bone, forming a key molecular chain in the early pathology of osteoarthritis.

3. Regulatory Role of PDGF-BB in Osteoarthritis Progression

The function of PDGF-BB was further verified using conditional gene knockout technology: In mice with specific knockout of PDGF-BB in preosteoclasts (PdgfbcKO) after DMM surgery, the number of CD31hiEmcnhi-positive blood vessels in subchondral bone was significantly reduced compared with wild-type mice, while the OARSI score was significantly decreased, and the degree of articular cartilage degeneration was effectively alleviated. Behavioral assessments showed that knockout mice had better active movement distance, activity time, and average speed than wild-type model mice, and the paw withdrawal threshold was increased, indicating improved pain symptoms.

In contrast, transgenic mice overexpressing PDGF-BB in preosteoclasts (PdgfbcTG) exhibited a spontaneous osteoarthritis phenotype. Five-month-old transgenic mice showed increased subchondral bone angiogenesis, abnormal bone structure remodeling, and articular cartilage degeneration without surgical intervention, with significantly increased OARSI scores. Immunohistochemical detection showed that the expression of cartilage degeneration markers such as Col10A1 and MMP-13 in articular cartilage of transgenic mice was upregulated, accompanied by obvious nerve ingrowth, further confirming that PDGF-BB overexpression is sufficient to drive the pathological process of osteoarthritis.

4. Research Significance and Prospects

This study is the first to confirm that PDGF-BB derived from preosteoclasts is a key factor driving pathological angiogenesis in subchondral bone during the pathogenesis of osteoarthritis. It promotes the cascade reaction of angiogenesis, cartilage degeneration, and nerve ingrowth by activating the pericyte PDGFR-β signaling pathway. This finding reveals the molecular mechanism of early pathology in osteoarthritis and establishes PDGF-BB as a potential target for early diagnosis and intervention of the disease.

Future studies need to further explore the upstream regulatory mechanism of PDGF-BB secretion by preosteoclasts after joint injury and clarify how factors such as mechanical load affect the expression regulation of PDGF-BB. At the same time, it is necessary to verify the correlation between PDGF-BB levels and osteoarthritis progression in clinical samples and evaluate the applicability of therapeutic strategies targeting the PDGF-BB/PDGFR-β signaling pathway in different subtypes of osteoarthritis, laying a foundation for the development of precise early intervention methods.

This article is reviewed and published by the technical expert team of UA

Disclaimer: This article partially utilizes artificial intelligence assistance in its creation. If any content involves copyright or intellectual property issues, please let us know and we promise to verify and remove it as soon as possible.

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