Mesenchymal progenitor cells from non-inflamed versus inflamed synovium post-ACL injury present with distinct phenotypes and cartilage regeneration capacity.

BACKGROUND: Osteoarthritis (OA) is a chronic debilitating disease impacting a significant percentage of the global population. While there are numerous surgical and non-invasive interventions that can postpone joint replacement, there are no current treatments which can reverse the joint damage occurring during the pathogenesis of the disease. While many groups are investigating the use of stem cell therapies in the treatment of OA, we still don't have a clear understanding of the role of these cells in the body, including heterogeneity of tissue resident adult mesenchymal progenitor cells (MPCs). METHODS: In the current study, we examined MPCs from the synovium and individuals with or without a traumatic knee joint injury and explored the chondrogenic differentiation capacity of these MPCs in vitro and in vivo. RESULTS: We found that there is heterogeneity of MPCs with the adult synovium and distinct sub-populations of MPCs and the abundancy of these sub-populations change with joint injury. Furthermore, only some of these sub-populations have the ability to effect cartilage repair in vivo. Using an unbiased proteomics approach, we were able to identify cell surface markers that identify this pro-chondrogenic MPC population in normal and injured joints, specifically CD82LowCD59+ synovial MPCs have robust cartilage regenerative properties in vivo. CONCLUSIONS: The results of this study clearly show that cells within the adult human joint can impact cartilage repair and that these sub-populations exist within joints that have undergone a traumatic joint injury. Therefore, these populations can be exploited for the treatment of cartilage injuries and OA in future clinical trials.

Tryptase ß regulation of joint lubrication and inflammation via proteoglycan-4 in osteoarthritis.

PRG4 is an extracellular matrix protein that maintains homeostasis through its boundary lubricating and anti-inflammatory properties. Altered expression and function of PRG4 have been associated with joint inflammatory diseases, including osteoarthritis. Here we show that mast cell tryptase ß cleaves PRG4 in a dose- and time-dependent manner, which was confirmed by silver stain gel electrophoresis and mass spectrometry. Tryptase-treated PRG4 results in a reduction of lubrication. Compared to full-length, cleaved PRG4 further activates NF-κB expression in cells overexpressing TLR2, -4, and -5. In the destabilization of the medial meniscus model of osteoarthritis in rat, tryptase ß and PRG4 colocalize at the site of injury in knee cartilage and is associated with disease severity. When human primary synovial fibroblasts from male osteoarthritis patients or male healthy subjects treated with tryptase ß and/or PRG4 are subjected to a quantitative shotgun proteomics and proteome changes are characterized, it further supports the role of NF-κB activation. Here we show that tryptase ß as a modulator of joint lubrication in osteoarthritis via the cleavage of PRG4.

Bone Mineral Density Changes in the Hip and Spine of Men and Women 1-Year After Primary Cemented Total Knee Arthroplasty: Prospective Cohort Study.

This study evaluated age- and sex-adjusted changes in total hip and spine bone mineral density (BMD) within 1 year of total knee arthroplasty (TKA) using a prospective, longitudinal cohort with a one-year follow-up. Preoperatively, subjects underwent routine bone mineral densitometry of their hip and spine, which was repeated 12 months postoperatively. Of 108 subjects, 97 (90%) completed BMD testing. Total hip BMD decreased significantly over time (1.80% change, P<0.001) with females losing more than males (P<0.001). The pattern was similar, but attenuated in the spine. Subjects undergoing primary cemented TKA had significant bone loss in the hip within 12 months, beyond that expected with age.