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Continuous passive motion applied to whole joints stimulates chondrocyte biosynthesis of PRG4.

ABSTRACT: Continuous passive motion (CPM) is currently a part of patient rehabilitation regimens after a variety of orthopedic surgical procedures. While CPM can enhance the joint healing process, the direct effects of CPM on cartilage metabolism remain unknown. Recent in vivo and in vitro observations suggest that mechanical stimuli can regulate articular cartilage metabolism of proteoglycan 4 (PRG4), a putative lubricating and chondroprotective molecule found in synovial fluid and at the articular cartilage surface.(1) Determine the topographical variation in intrinsic cartilage PRG4 secretion. (2) Apply a CPM device to whole joints in bioreactors and assess effects of CPM on PRG4 biosynthesis.A bioreactor was developed to apply CPM to bovine stifle joints in vitro. Effects of 24h of CPM on PRG4 biosynthesis were determined.PRG4 secretion rate varied markedly over the joint surface. Rehabilitative joint motion applied in the form of CPM regulated PRG4 biosynthesis, in a manner dependent on the duty cycle of cartilage sliding against opposing tissues. Specifically, in certain regions of the femoral condyle that were continuously or intermittently sliding against meniscus and tibial cartilage during CPM, chondrocyte PRG4 synthesis was higher with CPM than without.Rehabilitative joint motion, applied in the form of CPM, stimulates chondrocyte PRG4 metabolism. The stimulation of PRG4 synthesis is one mechanism by which CPM may benefit cartilage and joint health in post-operative rehabilitation.

SUBMITTER: Nugent-Derfus GE

PROVIDER: S-EPMC2680602 | biostudies-literature | 2007 May

REPOSITORIES: biostudies-literature

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Continuous passive motion applied to whole joints stimulates chondrocyte biosynthesis of PRG4.

Nugent-Derfus G E GE Takara T T O'neill J K JK Cahill S B SB Görtz S S Pong T T Inoue H H Aneloski N M NM Wang W W WW Vega K I KI Klein T J TJ Hsieh-Bonassera N D ND Bae W C WC Burke J D JD Bugbee W D WD Sah R L RL

Osteoarthritis and cartilage 20061208 5

<h4>Unlabelled</h4>Continuous passive motion (CPM) is currently a part of patient rehabilitation regimens after a variety of orthopedic surgical procedures. While CPM can enhance the joint healing process, the direct effects of CPM on cartilage metabolism remain unknown. Recent in vivo and in vitro observations suggest that mechanical stimuli can regulate articular cartilage metabolism of proteoglycan 4 (PRG4), a putative lubricating and chondroprotective molecule found in synovial fluid and at ...[more]

PMID: 17157538

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Project description:PurposeTo perform a systematic review of postoperative rehabilitation protocols for third-generation autologous chondrocyte implantation (ACI) of the knee joint.MethodsA systematic review was performed by searching PubMed, Cochrane Library, and EMBASE to locate randomized controlled trials that described a rehabilitation protocol following third-generation ACI of the knee joint. The search terms used were: "autologous" AND "chondrocyte" AND "randomized". Data extracted from each study included various components of postoperative rehabilitation, such as initial weight-bearing (WB) status and time to full WB, the use of continuous passive motion (CPM), the time to return to sports, and physical therapy (PT) modalities used and the timing of their initiation.ResultsTwenty-five studies (22 Level I, 3 Level II) met inclusion criteria, including a total of 905 patients undergoing treatment with ACI. The average patient age ranged from 29.1 to 54.8 years, and the mean follow-up time ranged from 3 months to 10.0 years. The average lesion size ranged from 1.9 to 5.8 cm2, and the most common lesion location was the medial femoral condyle (n = 494). Twenty studies allowed partial WB postoperatively with all studies permitting full WB within 12 weeks. Twenty studies used CPM in their rehabilitation protocols and initiated its use within 24 hours postoperatively. Among 10 studies that reported time to return to sport, 9 (90%) allowed return by 12 months. While most protocols used strength training as well as the inclusion of proprioceptive training, there was disagreement on the timing and inclusion of specific PT modalities used during the rehabilitation process.ConclusionsBased on the included studies, most rehabilitation protocols for third-generation ACI initiate CPM within 24 hours postoperatively and allow partial WB immediately following surgery with progression to full WB within 12 weeks. There is variation of the PT modalities used as well as the timing of their initiation.Level of evidenceLevel II, systematic review of Level I-II studies.

Project description:To gain insight into the effect of diabetes on fracture healing, experiments were carried out focusing on chondrocyte apoptosis during the transition from cartilage to bone. Type 1 diabetes was induced in mice by multiple low-dose streptozotocin injections, and simple transverse fractures of the tibia or femur was carried out. Large-scale transcriptional profiling and gene set enrichment analysis were performed to examine apoptotic pathways on total RNA isolated from fracture calluses on days 12, 16, and 22, a period of endochondral bone formation when cartilage is resorbed and chondrocyte numbers decrease. Tumor necrosis factor alpha (TNF-alpha) protein levels were assessed by ELISA and caspase-3 by bioactivity assay. The role of TNF was examined by treating mice with the TNF-specific inhibitor pegsunercept. In vitro studies investigated the proapoptotic transcription factor FOXO1 in regulating TNF-induced apoptosis of chondrogenic ATDC5 and C3H10T1/2 cells as representative of differentiated chondrocytes, which are important during endochondral ossification. mRNA profiling revealed an upregulation of gene sets related to apoptosis in the diabetic group on day 16 when cartilage resorption is active but not day 12 or day 22. This coincided with elevated TNF-alpha protein levels, chondrocyte apoptosis, enhanced caspase-3 activity, and increased FOXO1 nuclear translocation (p < .05). Inhibition of TNF significantly reduced these parameters in the diabetic mice but not in normoglycemic control mice (p < .05). Silencing FOXO1 using siRNA in vitro significantly reduced TNF-induced apoptosis and caspase activity in differentiated chondrocytes. The mRNA levels of the proapoptotic genes caspase-3, caspase-8, caspase-9, and TRAIL were significantly reduced with silencing of FOXO1 in chondrocytic cells. Inhibiting caspase-8 and caspase-9 significantly reduced TNF-induced apoptosis in chondrogenic cells. These results suggest that diabetes causes an upregulation of proapoptotic genes during the transition from cartilage to bone in fracture healing. Diabetes increased chondrocyte apoptosis through a mechanism that involved enhanced production of TNF-alpha, which stimulates chondrocyte apoptosis and upregulates mRNA levels of apoptotic genes through FOXO1 activation.

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Continuous passive motion applied to whole joints stimulates chondrocyte biosynthesis of PRG4.

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Continuous passive motion applied to whole joints stimulates chondrocyte biosynthesis of PRG4.

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