The Role of Osteopathic Practice in Multimodal Osteoarthritis Care of the Hip or Knee

BACKGROUND: Osteoarthritis (OA) is the second most prevalent cause of Musculoskeletal disorders, affecting 343 million people across the globe. Despite the nearly 50 non-pharmacological treatment modalities presented today, the research available, at present, omits incorporating osteopathic treatments into research protocols, and fails to contribute with evidence showing if treatments presented enhance the general effectiveness of rehabilitation in decreasing pain and disability in patients subjected to OA. METHODS: A literature review based on searches in the following databases: CINAHL, COCHRANE, OVID and PubMed were conducted. All data was processed by the authors independently and subsequently agreed on in terms of relevance for the objectives of the review. RESULT: Ultimately seven articles published between 2004 to 2018 were assessed. Three studies aimed to investigate interventions for OA of the knee alone, three involved both the osteoarthritic hip and knee, while one studied OA of the hip exclusively, but the main focus area remained the same, measuring pain severity and physical function. Six of them were randomized controlled trials, while one of them was a longitudinal study. CONCLUSION: Research suggests that OMT can have a beneficial effect in the management of hip and knee OA, however, the presence of osteopathic interventions is as of today very poor in research available and further research is needed to determine the effects of OMT in multimodal clinical practice

Specific targeting of PDGFR beta in the stroma inhibits growth and angiogenesis in tumors with high PDGF-BB expression

PDGF-BB/PDGFR beta signaling plays an important role during vascularization by mediating pericyte recruitment to the vasculature, promoting the integrity and function of vessels. Until now it has not been possible to assess the specific role of PDGFR beta signaling in tumor progression and angiogenesis due to lack of appropriate animal models and molecular tools. Methods: In the present study, we used a transgenic knock-in mouse strain carrying a silent mutation in the PDGFR beta ATP binding site that allows specific targeting of PDGFR beta using the compound 1-NaPP1. To evaluate the impact of selective PDGFR beta inhibition of stromal cells on tumor growth we investigated four tumor cell lines with no or low PDGFR beta expression, i.e. Lewis lung carcinoma (LLC), EO771 breast carcinoma, B16 melanoma and a version of B16 that had been engineered to overexpress PDGF-BB (B16/PDGF-BB). Results: We found that specific impairment of PDGFR beta kinase activity by 1-NaPP1 treatment efficiently suppressed growth in tumors with high expression of PDGF-BB, i.e. LLC and B16/PDGF-BB, while the clinically used PDGFR beta kinase inhibitor imatinib did not suppress tumor growth. Notably, tumors with low levels of PDGF-BB, i.e. EO771 and B16, neither responded to 1-NaPP1 nor to imatinib treatment. Inhibition of PDGFR beta by either drug impaired tumor vascularization and also affected pericyte coverage; however, specific targeting of PDGFR beta by 1-NaPP1 resulted in a more pronounced decrease in vessel function with increased vessel apoptosis in high PDGF-BB expressing tumors, compared to treatment with imatinib. In vitro analysis of PDGFR beta ASKA mouse embryo fibroblasts and the mesenchymal progenitor cell line 10T1/2 revealed that PDGF-BB induced NG2 expression, consistent with the in vivo data. Conclusion: Specific targeting of PDGFR beta signaling significantly inhibits tumor progression and angiogenesis depending on PDGF-BB expression. Our data suggest that targeting PDGFR beta in the tumor stroma could have therapeutic value in patients with high tumor PDGF-BB expression.Correction in: THERANOSTICS, Volume: 10, Issue: 16, Pages: 7406-7408, DOI: 10.7150/thno.48039</p