Physiochemical properties of copper doped calcium sulfate in vitro and angiogenesis in vivo.

Bone cements were prepared by mixing calcium sulfate and copper sulfate in various proportions. We examined physical and physicochemical properties of the copper doped calcium sulfates and the effects of the cements on angiogenesis in vivo. Rod shaped calcium sulfate crystals were visible by scanning electron microscopy in the cement that contained no copper sulfate, whereas plate-like crystals covered the surface of the cement with high copper content. After immersion of the cements in simulated body fluid (SBF) for 1 day, X-ray diffractometric analysis showed that gypsum precipitates had formed in the copper doped calcium sulfate. The compressive strength of the cements increased from 3.3 MPa for pure calcium sulfate to 6.4 MPa for samples with copper sulfate added. Calcium ion release was greatest from pure calcium sulfate, and the rate of copper ion release was higher for cements containing the most copper. We found that 6 weeks after implantation, more blood vessels had formed around the high copper cement than for the copper-free cement. Copper doped calcium sulfate appears to be useful for application to regenerative medicine including wound healing and bone tissue engineering.

SDF-1/CXCR4 axis coordinates crosstalk between subchondral bone and articular cartilage in osteoarthritis pathogenesis.

Crosstalk between subchondral bone and articular cartilage is considered a central feature of osteoarthritis (OA) initiation and progression, but its underlying molecular mechanism remains elusive. Meanwhile, specific administration of drugs in subchondral bone is also a great challenge during investigation of the process. We here explore the role of stromal cell-derived factor 1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4) axis in the crosstalk between subchondral bone and articular cartilage in OA pathogenesis, using osmotic infusion pumps implanted in tibial subchondral bone directly to ensure quantitative, continuous and steady drug delivery over the entire experiment. We found that increased SDF-1 in subchondral bone firstly induced subchondral bone deterioration by erroneous Mesenchymal Stem Cells (MSCs) recruitment and excessive bone resorption in anterior cruciate ligament transection (ACLT) mice. Deterioration of subchondral bone then led to the traverse of SDF-1 from subchondral bone to overlying cartilage. Finally, SDF-1 from underlying subchondral bone combined with CXCR4 in chondrocytes to induce articular cartilage degradation by promoting the shift of transforming growth factor-ß receptor type I (TßRI) in chondrocytes from activin receptor-like kinase 5 (ALK5) to activin receptor-like kinase 1 (ALK1). More importantly, specific inhibition of SDF-1/CXCR4 axis in ACLT rats attenuated OA by stabilizing subchondral bone microarchitecture, reducing SDF-1 in cartilage and abrogating the shift of TßRI in chondrocytes. Our data demonstrate that the SDF-1/CXCR4 axis may coordinate the crosstalk between subchondral bone and articular cartilage in OA pathogenesis. Therefore, specific inhibition of SDF-1/CXCR4 axis in subchondral bone or intervention in SDF-1 traverse may be therapeutic targets for OA.