Abstract
Articular cartilage is compressed with joint-loading and weight-bearing stresses, followed by a bulging of the tissue during times of off-loading. This loading and off-loading causes changes in water content, and thus alterations in osmotic pressure. Another unique characteristic of articular cartilage is that it has longitudinal depth: surface, middle, and deep zones. Since each zone is composed of unique components of highly negative extracellular matrices, each zone has a different level of osmotic pressure. It was unclear how changes in osmotic pressure affected chondrocyte matrix turnover in specific longitudinal zones. Therefore, we hypothesized that a change in extrinsic osmotic pressure would alter the production of extracellular matrices by zone-specific chondrocytes. We incubated spheroidal cartilage organoids, formed by specific longitudinal depth zone-derived chondrocytes, under different levels of osmotic pressure. We compared the gene expression and the immunohistology of the matrix proteins produced by the zone-specific chondrocytes. We found that high osmotic pressure significantly upregulated the transient expression of aggrecan and collagen type-II by all zone-derived chondrocytes (p < 0.05). At a high osmotic pressure, surface-zone chondrocytes significantly upregulated the expression of collagen type-I (p < 0.05), and middle- and deep-zone chondrocytes significantly upregulated matrix metalloproteinase-13 (p < 0.05). The spheroids, once exposed to high osmotic pressure, accumulated extracellular matrices with empty spaces. Our findings show that chondrocytes have zone-specific turnover of extracellular matrices in response to changes in osmotic pressure.
Highlights
Articular cartilage contains an abundant amount of negatively charged sulfated glycosaminoglycan in the extracellular matrix (ECM), resulting in significantly higher osmotic pressure (OP) than in other tissues [1,2]
surface zone (SZ) and middle zone (MZ) at low OP (Low-OP) expressed Col-2 at a simi5laorfo11r lower level when compared with the deep zone (DZ) control throughout the experiments
We previously demonstrated that chondrocytes isolated from a specific longitudinal depth zone in articular cartilage formed a spheroid expressing unique characteristics of the zone [10]
Summary
Articular cartilage contains an abundant amount of negatively charged sulfated glycosaminoglycan (e.g., chondroitin sulfate) in the extracellular matrix (ECM), resulting in significantly higher osmotic pressure (OP) than in other tissues [1,2]. Because of weight bearing and joint loading, articular cartilage exudes interstitial water into synovium space and suchondral bone, but absorbs the water from these tissues after the loadings [3]. This in- and outward-moving interstitial water has the potential to alter the volume of the cartilage tissue and to trigger changes in OP (∆OP) [4]. The damage to articular cartilage causes a loss of ECM macromolecules and results in ∆OP and osteoarthritis (OA) development over time [5]. CCoolllaaggeennttyyppeeIIII aanndd aaggggrreeccaann aarree pprroodduucceeddbbyy aallll zzoonneess,, ppaarrttiiccuullaarrllyy MMZZ. OOssmmoottiicc pprreessssuurree ooff ccuullttuurree mmeeddiiuumm wwaass cchhaannggeedd oorr mmaaiinnttaaiinneedd aatt ddaayyss 1100aanndd1133. LL iinnddiiccaatteess llooww-‐OOPP;; LLLL aanndd LLHH iinnddiiccaattee ccoonnttiinnuuoouussllyy llooww-‐OOPP aanndd cchhaannggeedd OOPP ffrroomm llooww ttoo hhiigghh aatt ddaayy 1100,, rreessppeeccttiivveellyy;; LLLLLL,, LLHHLL,, aanndd LLHHHH iinnddiiccaatteecoconntitninuuououslsylylolwow-O‐POfPorfo2r1 d21ayds,acyhsa, ncgheadngOePdfrOoPm flroowmtolohwightoathdigayh 1a0t fdolalyow1e0dfboyllocwhaendgebdy OchPafnrgoemdhOigPhftroomlowhiagthdtaoyl1o3w, aantddcahyan13g,edanOdPchfraonmgelodwOtPo fhriogmh altowdayto1h0ifgohlloawt dedayby10cofonltlionwuoedusblyy hciognht-iOnuPo, ruesslpyehcitgivhe‐lOy.P, respectively
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